Effect of long-term food restriction on pituitary sensitivity to cLHRH-I in broiler breeder females

The effect of long-term food restriction on the sensitivity of the pituitary to exogenously administered chicken luteinizing hormone releasing hormone I (cLHRH-I) was investigated in three groups of broiler breeder females fed ad libitum, fed a restricted quantity of food or fed a restricted quantity of food to obtain an intermediate body weight between those of the first two groups. At 16 weeks of age, basal FSH release was higher in ad libitum fed birds, culminating in ovarian development and subsequent oestradiol production by the small follicles. At this age, LH secretion was independent of ovarian feedback factors. In all groups, cLHRH-I was most active in releasing LH in intact and ovariectomized animals and, to a lesser extent, in releasing FSH in ovariectomized birds. At 39 weeks of age, basal FSH concentrations were similar among intact animals of all groups, whereas LH concentrations differed among groups, with higher values in the restricted birds. This food effect was enhanced in ovariectomized birds. Furthermore, the high response to cLHRH-I in the ovariectomized, restricted birds compared with the ad libitum, ovariectomized group suggests an improved sensitivity of the hypothalamic-pituitary axis. In conclusion, birds fed ad libitum showed the highest responsiveness to ovarian factors and to cLHRH-I in releasing FSH in the period before sexual maturity. No effect of amount of feeding could be observed for LH. However, during the egg laying period, LH release by cLHRH-I was highly dependent on amount of feeding and on ovarian feedback regulation. This finding indicates that the amount of feeding can modify the sensitivity of the pituitary to cLHRH-I, and possibly to gonadal hormones, during the laying period.     

The effects of food restriction and hypophysectomy on numbers of primordial follicles and concentrations of hormones in rats

Three experiments were done to examine the effects of food restriction, beginning at 21 days of age, on loss of primordial follicles and on concentrations of gonadotropins and sex steroids in rats. In Experiment 1, food restriction (FR) from 21 to 51-55 days of age had no effect on number of primordial follicles, but increased the plasma concentration (p less than 0.05) of follicle stimulating hormone (FSH). (p less than 0.05). In Experiment 2, comparisons were made of groups of rats (1) fed ad libitum (AL) (2) hypophysectomized at 21 days of age and fed ad libitum (AL-HY), (3) food restriction from 21 to 52-58 days of age (FR), and (4) food restriction with twice-daily injections of follicular fluid (FR-FF). Hypophysectomy was the only treatment that decreased the loss of primordial follicles (p less than 0.001). Concentrations of FSH were decreased in AL-HY and increased in FR and FR-FF rats (144 +/- 13, 53 +/- 15, 275 +/- 30 and 359 +/- 56 ng/ml in AL, AL-HY, FR and FR-FF rats, respectively). Concentrations of luteinizing hormone (LH) were lower (p less than 0.05) in AL-HY, FR and FR-FF rats than in AL rats. In Experiment 3, AL and FR rats were unilaterally ovariectomized (ULO) at 30 days of age. Blood samples were taken 5 days prior to ULO, at ULO and at 12 h, 5 days, and 22-28 days after ULO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered negative feedback response to ovariectomy and estrogen in prepubertal restricted-diet rats

Studies were conducted to explore the hypothesis that the delayed sexual maturation of female rats induced by reduced food intake (R) may result partially from an altered negative feedback response to estrogen. Animals were placed on 60% of normal food intake at 20 days of age. Controls (C) were fed ad libitum. Rats were used for three different experiments at 31-32 days of age. In Experiment I, rats were ovariectomized (OVX) and injected subcutaneously for 4 days with varying doses of estradiol benzoate (EB). They were killed the day after the last injection. In Experiment II, rats were ovariectomized and killed in groups at 4, 12, 24, 48, 72, and 120 h after OVX. In Experiment III, they were castrated and 1 wk later received a single injection of 0.5 microgram EB. Groups were killed at 1, 2, 4, 8, and 24 h after injection. Sera from all experiments were assayed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Results of Experiment I indicate that the efficacy of EB for suppressing LH, but not FSH, secretion is increased significantly in R rats. In Experiment II, OVX resulted in a delayed increase in serum LH, but not FSH, concentrations of R rats when compared to C animals. Results of Experiment III indicate a delayed, but more prolonged, suppression of LH secretion by EB in R rats when compared to C rats. Prolactin secretion, on the other hand, increased earlier in R rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of chronic food restriction and treatments with leptin or ghrelin on different reproductive parameters of male rats

The existence of a close relationship between energy status and reproductive function is well-documented, especially in females, but its underlying mechanisms remain to be fully unfolded. This study aimed to examine the effects of restriction of daily calorie intake, as well as chronic treatments with the metabolic hormones leptin and ghrelin, on the secretion of different reproductive hormones, namely pituitary gonadotropins and prolactin, as well as testosterone, in male rats. Restriction (50%) in daily food intake for 20 days significantly reduced body weight as well as plasma PRL and T levels, without affecting basal LH and FSH concentrations and testicular weight. Chronic administration of leptin to rats fed ad libitum increased plasma PRL levels and decreased circulating T, while it did not alter other hormonal parameters under analysis. In contrast, in rats subjected to 50% calorie restriction, leptin administration increased plasma T levels and reduced testis weight. Conversely, ghrelin failed to induce major hormonal changes but tended to increase testicular weight in fed animals, while repeated ghrelin injections in food-restricted males dramatically decreased plasma LH and T concentrations and reduced testis weight. In sum, we document herein the isolated and combined effects of metabolic stress (50% food restriction) and leptin or ghrelin treatments on several reproductive hormones in adult male rats. Overall, our results further stress the impact and complex way of action of different metabolic cues, such as energy status and key hormones, in reproductive function also in the male.     

24-Hour Changes in Circulating Prolactin,Follicle-Stimulating Hormone,Luteinizing Hormone,and Testosterone in Young Male Rats Subjected to Calorie Restriction

This work analyzes the effect of calorie restriction on the 24 h variation of pituitary-testicular function in young male Wistar rats by measuring the circulating levels of prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Control animals were provided an equilibrium calorie diet and the experimental animals a calorie-restriction diet equivalent to 66% of food restriction for four weeks starting on day 35 of life. Different groups of control and experimental rats were killed at 6 h intervals around the clock, beginning 1 h after light on (HALO). Compared to the control animals, the mean secretion of prolactin was augmented and that of LH and testosterone decreased in calorie-restricted rats, whereas FSH release remained unchanged. Significant changes in the 24 h secretory pattern of circulating prolactin, LH, and testosterone occurred in the calorie-restricted rats. These include the appearance of a second maximum of plasma prolactin at 21 HALO, blunting of the LH peak seen at 13 HALO, and phase-shift of the testosterone peak from 13 HALO in controls to 17 HALO in calorie-restricted rats. The significant positive correlation between individual LH and testosterone levels found in controls was no longer observed in calorie-restricted rats. Availability of nutrients presumably affects the mechanisms that modulate the circadian variation of the pituitary-gonadal axis in growing male rats.     

Differential effects of amount of feeding on cell proliferation and progesterone production in response to gonadotrophins and insulin-like growth factor I by ovarian granulosa cells of broiler breeder chickens selected for fatness or leanness.

Strain differences in reproductive performance were demonstrated between broiler breeder female chickens selected for growth (GL line) or for food conversion efficiency (FC line) and the improvement in reproductive performance due to feed restriction also differed significantly. Feed allowance effects on the maturation of ovarian follicles, the incidence of atresia and egg production differed between the two lines exposed to similar feeding protocols. Feed restriction reduced body weights significantly and to a similar extent in both GL and FC lines. The number of normal and atretic yellow follicles was significantly higher under ad libitum feeding and in GL line than it was in the FC line. In both lines, feed restriction decreased multiple ovulation and increased egg production. In culture, granulosa cells from the three largest follicles (F1, F2 and F3) increased progesterone production in response to LH, FSH and insulin-like growth factor I but responses were different between the GL and FC lines fed either ad libitum or restricted diets. Granulosa cells from the two or three largest follicles in GL and FC (ad libitum) lines produced similar amounts of progesterone in response to LH, FSH and insulin-like growth factor I whereas, in restricted birds, the progesterone production was of the rank order F1 > F2 > F3 in both lines. The responsiveness of the GL line fed ad libitum was higher for LH than for either FSH or insulin-like growth factor I but in the GL line fed a restricted diet, it was high for all the hormones. In the FC line, responses to LH, FSH or insulin-like growth factor I were high in ad libitum-fed birds, but low in birds fed a restricted diet for all hormones. Insulin-like growth factor I combined with LH or FSH significantly increased the progesterone production of granulosa cells from birds fed restricted diets of both lines and this effect increased with increasing follicular size. There was a lack of interaction between insulin-like growth factor I and LH or FSH in the regulation of progesterone production by birds of both lines fed ad libitum. Insulin-like growth factor alone or in combination with LH or FSH increased granulosa cell proliferation in birds fed ad libitum more than it did in birds fed restricted diets. The greater proliferation rate of granulosa cells of chickens fed ad libitum, in response to insulin-like growth factor I alone or in combination with gonadotrophins, leading to the simultaneous differentiation of two or three large follicles with high progesterone production in response to LH or insulin-like growth factor I, accelerates the rate of maturation of follicles. This may also be the major cause of erratic and multiple ovulations in broiler breeder female chickens fed ad libitum. In conclusion, insulin-like growth factor I, alone or in combination with LH or FSH, is an important component in the control mechanisms for follicular development in broiler breeder hens. It is this component that is targeted by feed allowance and inadvertently altered by selection for growth.     

24-hour changes in circulating prolactin, follicle-stimulating hormone, luteinizing hormone, and testosterone in young male rats subjected to calorie restriction

This work analyzes the effect of calorie restriction on the 24 h variation of pituitary-testicular function in young male Wistar rats by measuring the circulating levels of prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Control animals were provided an equilibrium calorie diet and the experimental animals a calorie-restriction diet equivalent to 66% of food restriction for four weeks starting on day 35 of life. Different groups of control and experimental rats were killed at 6 h intervals around the clock, beginning 1 h after light on (HALO). Compared to the control animals, the mean secretion of prolactin was augmented and that of LH and testosterone decreased in calorie-restricted rats, whereas FSH release remained unchanged. Significant changes in the 24 h secretory pattern of circulating prolactin, LH, and testosterone occurred in the calorie-restricted rats. These include the appearance of a second maximum of plasma prolactin at 21 HALO, blunting of the LH peak seen at 13 HALO, and phase-shift of the testosterone peak from 13 HALO in controls to 17 HALO in calorie-restricted rats. The significant positive correlation between individual LH and testosterone levels found in controls was no longer observed in calorie-restricted rats. Availability of nutrients presumably affects the mechanisms that modulate the circadian variation of the pituitary-gonadal axis in growing male rats.     

Effect of vitamin A deficiency upon gonadotropin response to gonadotropin-releasing hormone

There is a monotypic change in basal serum gonadotropin levels following retinol treatment of chronically vitamin A-deficient (VAD) male rats. The present study was undertaken to investigate the hypothesis that the specific increase in serum follicle-stimulating hormone (FSH) represents a change in gonadotrope responsiveness to gonadotropin-releasing hormone (GnRH). To this end, a test dose of GnRH was given to VAD rats pre-, 5 days post-, and 10 days postreplacement of vitamin A (PVA). In VAD rats, basal serum FSH and luteinizing hormone (LH) levels were higher than those of controls. Increased LH/testosterone ratios, both in basal levels and in the secretory response to GnRH, suggested Leydig cell hyporesponsiveness in VAD animals. Both the FSH and LH responses to GnRH were maximal at 1 h, declining thereafter. Although the absolute increments in FSH and LH 1 h after GnRH in VAD rats were greater than in controls, the percent increase in FSH tended to be lower in VAD rats and to increase after vitamin A replacement. The specific enhancement of FSH release PVA became evident only when assessing total secretion of FSH and LH after GnRH. Luteinizing hormone response to GnRH increased PVA, but not significantly, while FSH secretion after GnRH increased both 5 and 10 days PVA, times during which basal FSH levels were also increasing. These changes in FSH secretion could not be attributed either to increases in endogenous GnRH or to changes in testosterone or estradiol levels. Basal serum androgen binding protein levels, elevated in VAD animals, did not respond to the acute increases in FSH after GnRH and remained high PVA, suggesting no acute change in Sertoli cell function. Thus, the PVA increase in FSH secretion unmasks a partial inhibition of the gonadotrope present in the retinol-deficient, retinoic acid-fed male rat.     

Relation of endogenous opioid peptides and morphine to neuroendocrine functions.

Morphine and the endogenous opioid peptides (EOP) exert similar effects on the neuroendocrine system. When adminstered acutely, they stimulate growth hormone (GH), prolactin (PRL), and adrenocorticotropin (ACTH) release, and inhibit release of luteinizing hormone (LH), follicle stimulating hormone (FSH),and thyrotropin (TSH). Recent studies indicate that the EOP probably have a physiological role in regulating pituitary hormone secretion. Thus injection of naloxone (opiate antagonist) alone in rats resulted in a rapid fall in serum concentrations of GH and PRL, and a rise in serum LH and FSH, suggesting that the EOP help maintain basal secretion of these hormones. Prior administration of naloxone or naltrexon inhibited stress-induced PRL release, and elevated serum LH in castrated male rats to greater than normal castrate levels. Studies on the mechanisms of action of the EOP and morphine on hormone secretion indicate that they have no direct effect on the pituitary, but act via the hypothalamus. There is no evidence that the EOP or morphine alter the action of the hypothalamic hypophysiotropic hormones on pituitary hormone secretion; they probably act via hypothalamic neurotransmitters to influence release of the hypothalamic hormones into the pituitary portal vessels. Preliminary observations indicate that they may increase serotonin and decrease dopamine metabolism in the hypothalamus, which could account for practically all of their effects on pituitary hormone secretion.     

Pituitary hormones and growth retardation in rats raised at simulated high altitude (3800m).

Growth and the endocrine status of the pituitary and thyroid glands were studied in rats born and raised in a hypobaric chamber at a simulated high altitude of 3800 m (SHA); comparisons were drawn with similar rats at sea level. From birth until 40 days of age, SHA rats weighed significantly less than controls with the most striking growth impairment found in female SHA rats. Relative organ weights of anterior pituitary glands, ovaries and uteri from 40-day-old female SHA rats were significantly less than controls. Pituitary content of growth hormone (GH) was reduced in 40-day-old female SHA rats while the content of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were significantly increased over sea level controls. Plasma levels of GH, LH, FSH and thyrotropin (TSH) and pituitary TSH levels did not differ from control values. However, thyroidal uptake of 131I and plasma protein-bound 131I were significantly reduced in SHA rats as compared with controls. It is suggested that (1) the continuous exposure of developing female rats to hypoxia significantly impairs pituitary function and reproductive maturation, and (2) that despite other environmental factors acting on the developing organism at high altitude, growth retardation in rats born and raised at high altitudes is primarily a consequence of hypoxia.     

Age-dependent effect of Freund's adjuvant on 24-hour rhythms in plasma prolactin, growth hormone, thyrotropin, insulin, follicle-stimulating hormone, luteinizing hormone and testosterone in rats

The effect of Freund's adjuvant administration on 24-hour changes of plasma prolactin, growth hormone (GH), thyrotropin (TSH), insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were studied in young (2 months) and aged (18 months) male Wistar rats. Rats were injected s.c. with Freund's adjuvant or adjuvant's vehicle and, 18 days later, they were killed at 6 different time intervals throughout a 24-hour cycle to measure circulating hormone levels by specific RIAs. Young rats receiving adjuvant's vehicle exhibited significant time-of-day-dependent variations in plasma TSH, LH and testosterone, with maximal levels at 1300 h, 0100 h and 1700 h, respectively. Prolactin and insulin levels, analyzed globally in a factorial ANOVA, showed significant time-of-day changes with maximal levels at 1300 - 1700 h and 2100 h, respectively. The daily rhythms in plasma LH and testosterone found in young rats were not longer observed in Freund's adjuvant-injected rats, while as far as TSH, a second peak was observed at 0100 h after Freund's adjuvant administration. Twenty-four hour rhythms in circulating TSH, LH and testosterone were blunted in old rats receiving either Freund's adjuvant or its vehicle. Aged rats exhibited significantly higher circulating levels of prolactin, and lower levels of GH, TSH, FSH and testosterone. The results indicate that secretion of prolactin, GH, TSH, FSH and testosterone are age-dependent, as are the responses of TSH, LH and testosterone to Freund's adjuvant administration.     

Increase in pulsatile secretion of growth hormone during failure of catch-up growth following glucocorticoid-induced growth inhibition

The pattern of growth hormone (GH) secretion was determined in rats injected with cortisone acetate, 5 mg/rat/day subcutaneously, or with an equivalent volume of saline for 4 days from age 40 days. Cortisone injections resulted in inhibition of growth of body weight and tail length. During recovery the rats resumed a normal rate of growth but failed to show catch-up growth acceleration. From 17 to 27 days of recovery, plasma was sampled at 15-min intervals through the lights-on period, 06:00 to 18:00, via a catheter chronically implanted in the superior vena cava. During sampling each rat was housed singly in an insulated chamber, unrestrained, and with food and water ad lib. Cortisone-treated animals had a normal periodicity of GH plasma concentration, but they showed a reduction in values in the range of 50 to 99 ng/ml (P less than 0.01) and an increase of values in the range of 200 to 499 ng/ml (P less than 0.025) and above 1000 ng/ml (P less than 0.05). The area under the GH concentration curve of the cortisone-treated rats was significantly greater than that of the controls, 100.9 +/- 18.7 (mean +/- SE) units vs 55.3 +/- 7.4 (P less than 0.025). Thus, increased growth hormone secretion during the light phase persisted in spite of failure of catch-up growth acceleration. The findings indicate that the mechanism involved in GH release is linked to the catch-up growth control.     

24-hour changes in ACTH, corticosterone, growth hormone, and leptin levels in young male rats subjected to calorie restriction

Calorie restriction of young male rats increases plasma prolactin, decreases luteinizing hormone (LH) and testosterone, and disrupts their 24 h secretory pattern. To study whether this could be the consequence of stress, we examined the 24 h variations of plasma adrenocorticotropic hormone (ACTH) corticosterone, growth hormone (GH), leptin, and adrenal corticosterone. Rats were submitted to a calorie restriction equivalent to a 66% of usual intake for 4 weeks, starting on day 35 of life. Controls were kept in individual cages and allowed to eat a normal calorie regimen. Significantly lower ACTH levels were detected in calorie-restricted rats. Plasma corticosterone levels during the light phase of the daily cycle were significantly higher in calorie-restricted rats. Time-of-day variation in plasma ACTH and corticosterone levels attained significance in calorie-restricted rats only, with a maximum toward the end of the resting phase. The daily pattern of adrenal gland corticosterone mirrored that of circulating corticosterone; however, calorie restriction reduced its levels. Plasma ACTH and corticosterone correlated significantly in controls only. Calorie restriction decreased plasma GH and leptin, and it distorted 24 h rhythmicity. In a second study, plasma ACTH and corticosterone levels were measured in group-caged rats, isolated control rats, and calorie-restricted rats during the light phase of the daily cycle. Plasma ACTH of calorie-restricted rats was lower, and plasma corticosterone was higher, compared with isolated or group-caged controls. The changes in the secretory pattern of hormones hereby reported may be part of the neuroendocrine and metabolic mechanisms evolved to maximize survival during periods of food shortage.     

A role for inhibin in the control of follicle-stimulating hormone secretion in male rats

We examined the relationship of testosterone (T) and porcine follicular fluid (pFF) in the negative feedback control of FSH and LH secretion in adult male rats. Either at the time of castration (acute) or at least 30 days after castration (chronic), we implanted T-filled Silastic capsules, which were 2 mm, 10 mm, or 30 mm long; empty capsules (30 mm) served as controls. Seven days later, we injected either 0.15 ml of pFF or saline (i.v.), decapitated the rats 6 hours later, and collected trunk blood for subsequent serum analysis of FSH, LH, and T by RIA. In the acute groups, T implants suppressed the postcastration rises in plasma FSH and LH levels in a dose-dependent manner, with only the largest implant, 30 mm, able to return them to intact levels. PFF injection significantly suppressed FSH levels in intact and acute rats but had no effect on serum LH. In chronic rats, T therapy for 7 days suppressed plasma LH levels in a dose-dependent relationship, yet did not do so to plasma FSH levels. FSH levels were significantly higher in rats with the 30 mm T implants than in intact rats, but were significantly suppressed as compared to chronic controls. PFF significantly suppressed serum FSH levels in all chronic groups with the chronic controls showing the greatest amount of suppression. We conclude that the role for inhibin in the normal control of FSH secretion is that of a secondary modulator which is superimposed on, yet independent of, the steroid feedback mechanism. At any given moment this modulation is dependent upon the secretory activity of the FSH gonadotrope.     

A Mathematical Model for the Actions of Activin,Inhibin, and Follistatin on Pituitary Gonadotrophs

The timed secretion of the luteinizing hormone (LH) and follicle stimulating hormone (FSH) from pituitary gonadotrophs during the estrous cycle is crucial for normal reproductive functioning. The release of LH and FSH is stimulated by gonadotropin releasing hormone (GnRH) secreted by hypothalamic GnRH neurons. It is controlled by the frequency of the GnRH signal that varies during the estrous cycle. Curiously, the secretion of LH and FSH is differentially regulated by the frequency of GnRH pulses. LH secretion increases as the frequency increases within a physiological range, and FSH secretion shows a biphasic response, with a peak at a lower frequency. There is considerable experimental evidence that one key factor in these differential responses is the autocrine/paracrine actions of the pituitary polypeptides activin and follistatin. Based on these data, we develop a mathematical model that incorporates the dynamics of these polypeptides. We show that a model that incorporates the actions of activin and follistatin is sufficient to generate the differential responses of LH and FSH secretion to changes in the frequency of GnRH pulses. In addition, it shows that the actions of these polypeptides, along with the ovarian polypeptide inhibin and the estrogen-mediated variations in the frequency of GnRH pulses, are sufficient to account for the time courses of LH and FSH plasma levels during the rat estrous cycle. That is, a single peak of LH on the afternoon of proestrus and a double peak of FSH on proestrus and early estrus. We also use the model to identify which regulation pathways are indispensable for the differential regulation of LH and FSH and their time courses during the estrous cycle. We conclude that the actions of activin, inhibin, and follistatin are consistent with LH/FSH secretion patterns, and likely complement other factors in the production of the characteristic secretion patterns in female rats.     

Effects of intermittent pulsatile infusion of luteinizing hormone-releasing hormone on dihydrotestosterone-suppressed gonadotropin secretion in castrate rams

The feedback effects of dihydrotestosterone (DHT) on gonadotropin secretion in rams were investigated using DHT-implanted castrate rams (wethers) infused with intermittent pulsatile luteinizing hormone-releasing hormone (LHRH) for 14 days. Castration, as anticipated, reduced both serum testosterone and DHT but elevated serum LH and follicle-stimulating hormone (FSH). Dihydrotestosterone implants raised serum DHT in wethers to intact ram levels and blocked the LH and FSH response to castration. The secretory profile of these individuals failed to show an endogenous LH pulse during any of the scheduled blood sampling periods, but a small LH pulse was observed following a 5-ng/kg LHRH challenge injection. Dihydrotestosterone-implanted wethers given repeated LHRH injections beginning at the time of castration increased serum FSH and yielded LH pulses that were temporally coupled to exogenous LHRH administration. While the frequency of these secretory episodes was comparable to that observed for castrates, amplitudes of the induced LH pulses were blunted relative to those observed for similarly infused, testosterone-implanted castrates. Dihydrotestosterone was also shown to inhibit LH and FSH secretion and serum testosterone concentrations in intact rams. In summary, it appears that DHT may normally participate in feedback regulation of LH and FSH secretion in rams. These data suggest androgen feedback is regulated by deceleration of the hypothalamic LHRH pulse generator and direct actions at the level of the adenohypophysis.     

Median eminence lesions reveal separate hypothalamic control of pulsatile follicle-stimulating hormone and luteinizing hormone release

The effects of hypothalamic lesions designed to destroy either the anterior median eminence (ME) or the posterior and mid-ME on pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined in castrated male rats. In sham-operated animals, mean plasma FSH concentrations rose to peak at 10 min after the onset of sampling, whereas LH declined to a nadir during this time. In the final sample at 120 min, the mean FSH concentrations peaked as LH decreased to its minimal value. In rats with anterior ME lesions, there was suppression of LH pulses with continuing FSH pulses in 12 of 21 rats. On the other hand, in animals with posterior to mid-ME lesions, 3 out of 21 rats had elimination of FSH pulses, whereas LH pulses were maintained. Fifteen of 42 operated rats had complete ME lesions, and pulses of both hormones were abolished. The remaining 12 rats had partial ME lesions that produced a partial block of the release of both hormones. The results support the concept of separate hypothalamic control of FSH and LH release with the axons of the putative FSH-releasing factor (FSHRF) neuronal system terminating primarily in the mid- to caudal ME, whereas those of the LHRH neuronal system terminate in the anterior and mid-median eminence. We hypothesize that pulses of FSH alone are mediated by release of the FSHRF into the hypophyseal portal vessels, whereas those of LH alone are mediated by LHRH. Pulses of both gonadotropins simultaneously may be mediated by pulses of both releasing hormones simultaneously. Alternatively, relatively large pulses of LHRH alone may account for simultaneous pulses of both gonadotropins since LHRH has intrinsic FSH-releasing activity.     

Effects of dietary zinc deficiency on gonadotrophin secretion and testicular growth in young male sheep.

The hypothesis that the secretion of gonadotrophins would be reduced by zinc deficiency was tested in five groups of four young Merino rams (initial liveweight 22 kg). Four groups were fed ad libitum with diets containing 4, 10, 17 or 27 micrograms Zn g-1. The effects of loss of appetite on the deficient diet was controlled by feeding a fifth group (pair-fed control) at a rate of 27 micrograms Zn g-1, but the amount of feed offered was restricted to that eaten voluntarily by the deficient (4 micrograms Zn g-1) group. Blood was sampled every 20 min for 32 h on two occasions before the treatments were imposed and 96 days later, at the end of the experiment. The rams were injected with gonadotrophin-releasing hormone (GnRH; 10 ng kg-1 i.v.) after each serial sampling, and with naloxone (1 mg kg-1 i.v.) 24 h after the end of the final GnRH test. In the group that were fed the diet with the lowest zinc content, the concentration of zinc in blood plasma was reduced to 18% of that in the pair-fed controls (P < 0.05) and was within the deficient range. The appetite of the deficient rams was half that of the controls fed 27 micrograms Zn g-1 ad libitum and there was no increase in liveweight or testicular diameter during pubertal development. Similar, but smaller, effects were observed in the pair-fed controls. There were no significant differences between pair-fed and deficient groups in the frequency of the luteinizing hormone (LH) pulses or in the concentration of follicle-stimulating hormone (FSH), but the secretion of gonadotrophins was markedly lower in both groups than in the control rams fed ad libitum. The response to GnRH was not affected by treatment, but the increase in LH pulse frequency evoked by naloxone was lower in the deficient animals than in other groups. The animals fed zinc at intermediate rates (10-17 micrograms g-1) showed similar responses to the controls fed ad libitum. It is concluded that the specific effects of zinc deficiency on testicular function were small. Most of the reduction in testicular growth in rams fed a deficient diet was not specifically related to the trace element, but was due to the fall in energy and protein intake caused by the loss of appetite. This leads to a reduction in the frequency of GnRH pulses secreted by the hypothalamus, and to low rates of gonadotrophin secretion by the pituitary gland.     

Ontogeny of growth hormone, prolactin, luteinizing hormone, and testosterone secretory patterns in the ram

The ontogenetic changes that occur in secretory patterns of growth hormone (GH), prolactin (Prl), luteinizing hormone (LH), and testosterone (T) in rams maintained in constant photoperiod were examined. Nine ram lambs were moved to individual pens in a controlled environment (12L: 12D cycle; 18-24 degrees C temperature) at 66 days of age. Blood samples were collected via indwelling cannulae at 15-min intervals for an 8-h period at 80, 136, 192, 248, and 304 days of age. Plasma concentrations of GH, Prl, LH, and T were quantitated and parameters of the secretory patterns determined. Mean concentration of GH tended to decline with age, probably because the amplitude of secretory peaks was significantly reduced with age. There were no age-associated changes in basal concentration of GH or incidence of GH peaks. There was an increase in Prl secretion (as estimated by mean concentration) at 136 and after 248 days of age. Significant age-associated changes occurred in all parameters of LH and T secretion. At the younger ages, testosterone concentrations were low and LH concentrations were elevated. At the older ages the relationship was reversed, with LH low and testosterone high. There were no significant correlations between frequency and magnitude of LH and T peaks. The significant correlations present among parameters of LH and T secretion were between basal concentration of LH and overall mean concentration and basal concentration of T. These results suggest that LH may not be the sole tropic stimulator of acute T secretion.     

Rhythmic and Nonrhythmic Modes of Anterior Pituitary Gland Secretion

Because of confounding effects of subject-specific and hormone-specific metabolic clearance, the nature of anterior pituitary secretory events in vivo is difficult to ascertain. We review an approach to this problem, in which deconvolu-tion analysis is used to dissect the underlying secretory behavior of an endocrine gland quantitatively from available serial plasma hormone concentration measurements assuming one- or two-compartment elimination kinetics. This analytical tool allows one to ask the following physiological questions: (a) does the anterior pituitary gland secrete exclusively in randomly dispersed bursts, and/or does a tonic (constitutive) mode of interburst hormone secretion exist? and (b) what secretory mechanisms generate the circadian or nyctohemeral rhythms in blood concentrations of pituitary hormones? Waveform-independent deconvolution analysis of 24-h serum hormone concentration profiles of immunoreactive growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and β-endorphin in normal men sampled every 10 min showed that (a) anterior pituitary gland secretion in vivo occurs in an exclusively burstlike mode for all hormones except TSH and prolactin (for the latter two, a mixed burst and basal mode pertains); (b) significant nyctohemeral regulation of secretory burst frequency alone is not demonstrable for any hormone; (c) prominent 24-h variations in secretory-burst amplitude alone are delineated for ACTH and LH; (d) TSH, GH, and β-endorphin are both frequency and amplitude controlled; (e) prolactin manifests 24-h rhythms in both secretory-burst amplitude and nadir secretory rates; (f) no significant diurnal variations occur in FSH secretory parameters; and (g) a fixed hormone half-life yields good fits of the 24-h serum hormone concentration series, which indicates that there is no need to introduce diurnal variations in hormone half-lives. In summary, the normal human anterior pituitary gland appears to release its various (glyco)protein hormones via intermittent secretory episodes that are apparently unassociated with significant basal hormone secretion, except in the case of TSH and prolactin. Hormone-specific amplitude and/or frequency control of secretory burst activity over 24 h provides the mechanistic basis for the classically recognized nyctohemeral rhythms in plasma concentrations of adenohypophyseal hormones in the human.