Catecholamine mechanisms in the feedback effects of estradiol benzoate on the release of LH and prolactin

The role of hypothalamic catecholamines and luteinizing hormone releasing hormone (LHRH) in the negative feedback effect of estradiol benzoate (EB) on luteinizing hormone (LH) release was studied in chronic ovariectomized rats. Administration of 10 micrograms EB decreased plasma LH levels and increased LHRH content in the medial basal hypothalamus (MBH) 1 day after injection. Inhibition of dopamine and norepinephrine synthesis with alpha-methyl-p-tyrosine (alpha-MT) reduced the LHRH content in the MBH in both oil- and EB-treated animals and partially reversed the decrease in plasma LH levels. Inhibition of norepinephrine synthesis with fusaric acid decreased LHRH content in both oil- and EB-treated rats but had no effect on plasma LH levels. The results suggest that at least a portion of the inhibitory effect of EB on LH release is due to the stimulation of an inhibitory dopaminergic mechanism which reduces LHRH release from the MBH. This feedback mechanism is apparently not susceptible to dopaminergic receptor blockade since administration of pimozide had no effect on LH levels. The stimulatory feedback effect of EB on prolactin release was studied in the same animals. alpha-MT and EB produced additive effects on plasma prolactin levels whereas fusaric acid blocked the EB-induced increase in plasma prolactin levels. Pimozide appeared to potentiate the effect of EB on prolactin release. The results reconfirm the possible role of noradrenergic neurons in the release of prolactin induced by EB and also suggest that EB stimulates a dopaminergic mechanism which is inhibitory to prolactin release but is normally masked by increased noradrenergic activity.     

Aspects of the neuroendocrine control of ovulation and broodiness in the domestic hen

The neuroendocrine control of ovulation and broodiness in the domestic hen involves complex interactions between hypothalamic neuropeptides, neurotransmitters, and ovarian steroids which regulate the secretion of luteinizing hormone (LH) and prolactin. Nuclear progesterone receptor is localized in many neurons throughout the hypothalamus but is absent from LHRH neurons. Hence, the positive feedback action of progesterone on LH release is not mediated by a genomic mechanism within the LHRH neuron. Precursors of 5-hydroxytryptamine (5HT) and dopamine (DA) inhibit the preovulatory release of LH, while the turnover rates of these neurotransmitters in the anterior hypothalamus decrease when preovulatory levels of LH are at their highest. Further, a population of receptors for 5HT which occurs in the anterior hypothalamus in laying birds is absent in nonlaying, incubating hens. Taken together, these observations suggest that the preovulatory surge of LH is mediated by a transitory decrease in the inhibitory action of 5HT and possibly DA, on the secretion of LHRH. Neurons containing 5HT may play a role in the regulation of prolactin release and, more specifically, in the control of broodiness. Drugs which enhance the function of 5HT neurons stimulate prolactin release while increased prolactin secretion in incubating hens is associated with an increase in the turnover of 5HT in the anterior hypothalamus. No receptors for 5HT were demonstrable in the anterior pituitary gland, showing that the prolactin-releasing activity of 5HT must be mediated by a prolactin-releasing factor (PRF). A candidate for a physiological PRF is vasoactive intestinal polypeptide (VIP).(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of hypothalamic LHRH, pituitary LH and plasma LH in developing rats.

Hypothalamic LHRH, pituitary LH and plasma LH levels were measured in rats of both sexes from day 5-60 after birth. The content of hypothalamic LHRH was very high in one-week-old male and female rats. It declined gradually till day 17 in the female rat and sharply on day 10 in the male rat. Subsequently the content of hypothalamic LHRH increased and showed peak values on day 25 in the female rat and on day 45 in the male rat. It decreased markedly at respective times of puberty in both sexes (day 37 in the female rat and day 52-60 in the male rat). Results of the study suggest that maturation of hypothalamo-hypophyseal-axis proceeds in three distinct stages. Observations on days 17, 25 and 37 in the female rat and on days 5, 7, 10 and 22 in the male rat clearly show an inverse relationship between hypothalamic LHRH and plasma LH and a parallel relationship between pituitary and plasma LH. Marked decline in the content of hypothalamic LHRH at respective times of puberty in both sexes indicates that the release of threshold levels of LHRH from the hypothalamus may apparently be the event initiating the pubertal changes in rat.     

The effect of luteinizing hormone releasing hormone on the copulatory behavior of hyperprolactinemic male rats

The present study was undertaken to test the hypothesis that the deficits in copulatory behavior observed in hyperprolactinemic male rats may be related to a reduction in hypothalamic release of luteinizing hormone releasing hormone (LHRH). Adult male Fischer 344 rats were made hyperprolactinemic by ectopic pituitary grafts or were sham operated and 30 min prior to being tested for copulatory performance received a single subcutaneous injection of 500 ng LHRH, 100 ng LHRH, or saline. On different occasions, testosterone (T) levels were measured in plasma collected 30 min following identical treatments. Plasma prolactin (PRL) levels were determined in samples collected 30 min after injection of 500 ng LHRH. Pituitary grafting produced the expected, significant increase in plasma PRL levels and significant deficits in copulatory behavior. Treatment of hyperprolactinemic subjects with 500 ng LHRH significantly reduced both the time to first intromission and the time to ejaculation to times comparable with those of sham-operated subjects. The 100-ng dose produced a significant reduction in mount frequency. Plasma T levels were significantly elevated following either dose of LHRH. These results demonstrate that exogenous LHRH can restore normal copulatory performance in hyperprolactinemic male rats and support the hypothesis that a reduction in hypothalamic LHRH release is responsible for the behavioral deficits observed in those animals.     

Effects of short photoperiod on the ability of golden hamster pituitaries to secrete prolactin and gonadotropins in vitro

Transfer of male golden (Syrian) hamsters from a 14L:10D (light:dark) to a 5L:19D photoperiod induced significant changes in pituitary function tested in vitro. Within 27 days after transfer to a 5L:19D photoperiod, basal prolactin (Prl) release was significantly depressed and response to dopamine (DA) was significantly enhanced as compared to Prl release by pituitaries from 14L: 10D hamsters. Follicle-stimulating hormone (FSH) release tended to be depressed after 9 or 27 days of 5L:19D exposure, but the effect was not significant. After 77 days of 5L:19D exposure, Prl release was further suppressed, while FSH release surpassed that seen in 14L:10D pituitaries. In vitro FSH response to luteinizing hormone releasing hormone (LHRH) was also enhanced at this time. After 15 weeks of exposure to a short photoperiod, FSH secretion was still elevated above control levels, but Prl release and Prl response to DA were no longer different from that of 14L: 10D controls. Secretion of luteinizing hormone (LH) in vitro, either basal or LHRH stimulated, was not affected by photoperiod at any time tested. From these results, we conclude that short photoperiod exposure does not reduce the pituitary's ability to secrete LH or FSH, although secretion of Prl is severely attenuated.     

Detrimental effects of short-term ethanol exposure on reproductive function in the female rat

To more completely assess the means by which alcohol impairs the female reproductive cycle in rats, we have measured hypothalamic luteinizing hormone-releasing hormone (LHRH), pituitary LHRH receptor content, and the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (Prl), and progesterone (P). After two successive cycles, the animals began receiving either an alcohol or a isocaloric control liquid diet regimen beginning on the first day of diestrus, with continued monitoring of the estrous cycle throughout the experiment. An additional set of controls consisted of animals maintained on lab chow and water provided ad libitum. Our results indicate that those animals receiving the control diets showed uninterrupted estrous patterns, whereas those animals receiving the alcohol diet remained in diestrus. Additionally, the alcohol-treated animals showed an increase (p less than 0.05) in LHRH content, with a concomitant decrease (p less than 0.01) in serum LH, and an increase (p less than 0.01) in serum Prl. No significant differences were detected in serum FSH levels or pituitary LHRH receptor content. No differences were detected in serum P levels. These results indicate that short-term alcohol administration disrupts the female reproductive cycle, causing persistent diestrus, and support our hypothesis that the alcohol-induced depression in serum LH levels is due to a diminished release rate of hypothalamic LHRH.     

Pulsatile infusion of luteinizing hormone-releasing hormone induces precocious puberty (vaginal opening and first ovulation) in the immature female guinea pig

Previously we have hypothesized that an increase in luteinizing hormone-releasing hormone (LHRH) due to hypothalamic maturation is the key factor controlling the onset of puberty. This led to the working hypothesis that precocious puberty would be induced if LHRH is administered with an appropriate protocol. Thus, effects of pulsatile infusion of LHRH on the onset of first vaginal opening and first ovulation in immature female guinea pigs were studied. Luteinizing hormone-releasing hormone in hourly pulses of either 5 ng or 50 ng was infused through a chronically implanted jugular catheter for 9-29 days starting at 20 days of age. For the control experiment saline was infused in a similar manner. Infusion of 5 ng LHRH/h resulted in significantly earlier (P less than 0.001) ages at first vaginal opening (24.7 +/- 0.9 days) and at first ovulation (28.8 +/- 0.9 days) compared to saline controls (first vaginal opening 53.3 +/- 6.8 days; first ovulation 55.2 +/- 6.5 days). Infusion with a 10-fold higher LHRH dose (50 ng/h) also advanced the age at first vaginal opening (25.3 +/- 0.7 days), but precocious ovulation was no longer induced (53.7 +/- 5.3 days). Interestingly, LHRH infusion with the high dose resulted in a prolonged period of vaginal opening and cornification without ovulation. These results indicate that 1) pulsatile infusion of a small amount of LHRH with a constant frequency induces precocious puberty in a laboratory rodent, and 2) infusion of LHRH with a dose higher than the effective dose for the induction of early puberty results in a persistent estrous anovulatory syndrome. Therefore, the present study not only supports our hypothesis that an increase in endogenous LHRH release is responsible for the onset of puberty, but also further suggests that excessive release of LHRH or abnormal patterns of LHRH release may be involved in the etiology of the anovulatory persistent estrus syndrome.     

Neuroendocrine control of ovulation

Modern methods of diagnosis have made the distinction between hypothalamic failure and ovarian failure routine. Failure of the orderly progression of hypothalamic gonadotrophin-releasing hormone (GnRH) → pituitary gonadotrophins → ovarian steroids and inhibin → hypothalamus/pituitary results in anovulation/amenorrhea. The hypothalamic connections that regulate the pattern and amplitude of GnRH pulses are plastic and respond to external/psychological conditions and internal/metabolic factors that may affect the hypothalamic substrate on which estrogen levels can act. We trace the neuroendocrine regulation of the ovarian cycle, concentrating on hypothalamic connections that underlie negative and positive feedback control of GnRH and the complementary role of the adenohypophysis. The main hormone regulating this "central axis" and the development of the endometrium is estradiol which is exported from the developing ovarian follicles and thereby closes the feedback loop with follicle development. Progesterone and inhibin are also involved. Neuroendocrine responses to internal and external factors can cause anovulation and amenorrhea. Generally, these are accompanied by abnormal negative feedback between estradiol and the gonadotrophins; coexistence of low estradiol and luteinizing hormone/follicle-stimulating hormone. There are three main causes: (1) genetic diseases that interfere with the migration of GnRH cells into the brain or result in misfolding of GnRH; (2) input from the brain that interrupts normal feedback (e.g. stress and weight loss amenorrhea); and (3) the effect of agents which alter central neurotransmission and hypothalamic function (e.g. elevated prolactin and psychotropic medications). All types of hypothalamic insufficiency result in insufficient stimulation of the ovaries. In addition to amenorrhea, this central alteration also results in other complications (downstream disease) that make hypothalamic amenorrhea of greater consequence than simply reproductive failure. Thus, there may be more at stake in the diagnosis and treatment of hypothalamic failure than brings the patient to her caregiver.     

Changes in prolactin levels caused by luteinizing hormone releasing hormone

The acute effects of luteinizing hormone releasing hormone (LHRH) on the release of prolactin (PRL) were investigated in 12 normal cycling women and 42 women with various menstrual disorders. LHRH (100 micrograms) was bolusly injected intramuscularly and PRL levels were measured immediately before the injection and at 30 minutes and 60 minutes after the injection. LHRH elicited an increase of more than 25% in PRL levels in 15 cases (27.8%) at both 30 minutes and 60 minutes after the injection, whereas PRL levels were decreased by more than 25% in 7 cases (13.0%). The PRL response to LHRH seemed to be related to basal PRL levels. Especially when the PRL concentration was 20 ng/ml or more, LHRH decreased PRL levels in 7 cases out of 16. On the other hand, LHRH increased PRL levels in the majority of cases with a PRL concentration less than 20 ng/ml. In conclusion, the LHRH injection occasionally alters PRL levels in either a positive or negative manner, depending upon the basal PRL levels.     

Age-related changes in the suppression of serum luteinizing hormone by estradiol-17beta in developing steers

Serum luteinizing hormone (LH) concentrations were measured at 4, 6, 8 and 10 mo of age in estradiol-17beta (E(2))-treated (n = 4) and contemporary control steers (n = 4). Serum LH was measured in samples collected at 30-min intervals starting at 0600 h for 12 h and for an additional 6 h following luteinizing hormone-releasing hormone (LHRH) injection. Estradiol-17beta suppressed mean serum LH concentrations at all ages (P<0.01), but it suppressed pulsatile release of LH only at 4 and 6 mo (P<0.01), not 8 and 10 mo of age. Luteinizing hormone release in response to LHRH, expressed as the area under the secretory curve, was larger and LH concentrations returned to pre-LHRH levels later in E(2)-treated steers (P<0.01). Peak LH concentrations after LHRH varied with age (P<0.05) but not E(2) treatment. These results suggest that E(2) suppression of LH in steers occurs at the hypothalamic level and developmental changes take place within the hypothalamicpituitary axis in absence of androgen feedback from the testis.     

Effect of [D-Trp6]LHRH infusion on prolactin secretion by perifused rat pituitary cells

The effect of a superactive agonistic analog of luteinizing hormone-releasing hormone (LHRH), [D-Trp6]LHRH on prolactin (PRL) secretion by perifused rat pituitary cells was investigated. Constant infusion of [D-Trp6]LHRH (0.5 ng/min) for 2-3 h elicited a significant decrease in PRL secretion by these cells. This decrease in PRL release started ca. 30 min after the beginning of the infusion with the LHRH analog and lasted up to 1.5-2 h. [D-Trp6]LHRH significantly stimulated luteinizing hormone (LH) secretion during the first 30 min of peptide infusion; thereafter, LH levels began to return to control values. In animals pretreated in vivo with 50 micrograms of [D-Trp6]LHRH (s.c.) 1 h before sacrifice, PRL secretion by the rat pituitary cell perifusion system was significantly lower than vehicle-injected controls throughout the entire [D-Trp6]LHRH infusion period. On the other hand, thyrotropin-releasing hormone (TRH)-stimulated PRL secretion was slightly, but significantly imparied by [D-Trp6]LHRH infusion, while dopamine (DA) inhibition of PRL release was unaffected by this same treatment. These results reinforce previous observations of a modulatory effect of [D-Trp6]LHRH, probably mediated by pituitary gonadotrophs, on PRL secretion by the anterior pituitary. In addition, our findings suggest that basal PRL secretion by the lactotroph may be dependent on a normal function of the gonadotroph. The collected data from this and previous reports support the existence of a functional link between gonadotrophs and lactotrophs in the rat pituitary gland.     

Endocrine mechanisms of puberty in heifers. Role of hypothalamo-pituitary estradiol receptors in the negative feedback of estradiol on luteinizing hormone secretion

The hypothesis tested was that the decline in negative feedback of estradiol on secretion of luteinizing hormone (LH) that occurs as puberty approaches in heifers results from a decline in the number of receptors for estradiol in the hypothalamus and/or pituitary. In addition, associated changes in receptors for luteinizing hormone-releasing hormone (LHRH) in the pituitary, ovarian follicle development, and uterine growth were characterized. Fifty prepubertal heifers, 234 to 264 days of age, were used. Six heifers of median body weight were designated controls, and sequential blood samples were collected at 20-min intervals for 24 h every 2 wk from 249 days of age through puberty and analyzed for concentrations of LH. Frequency of LH pulses/24 h was regressed on number of days prepuberty to develop a prediction equation for puberty. Thirty of the remaining 44 heifers were killed at 253, 302, and 351 days of age (n = 10/group), and tissues for described analyses were collected. Three to 5 days before tissue collection, sequential blood samples were obtained from these heifers, as described for control heifers to determine frequency of release of LH. With this information, number of days prepuberty at the time of tissue collection was estimated from the prediction equation developed with data from control heifers. The average age at puberty in control heifers was 366 days. The average age at puberty of heifers that were not killed or included in the control group (n = 14) was 360 days. Receptor and morphological data were related to the estimated onset of puberty. Cytosolic concentration of receptors for estradiol (fmoles receptor/mg cytosolic protein) in the anterior hypothalamus, medial basal hypothalamus, and anterior pituitary declined (p less than 0.05) as puberty approached. No change in concentration of receptors for estradiol was observed in the stalk median eminence or preoptic area. The concentration of receptors for LHRH in the anterior pituitary did not change as puberty approached. Uterine weight increased rapidly during the 50 days preceding puberty. The number of small, medium, or large follicles and the wet, pressed, or dry weight of the ovaries did not change as puberty approached. Follicles with a diameter greater than 12 mm were found only in the 3 heifers estimated to be closest to puberty at the time of tissue collection. The hypothesis that the decline in estradiol feedback on secretion of LH during the prepubertal period in heifers may result from a decline in the concentration of binding sites for estradiol at the hypothalamus and/or pituitary is supported by this study.     

Oestrogen and progesterone interactions in the control of gonadotrophin and prolactin secretion

Oestrogen and progesterone have marked effects on the secretion of the gonadotrophins and prolactin. During most of the oestrous or menstrual cycle the secretion of gonadotrophin is maintained at a relatively low level by the negative feedback of oestrogen and progesterone on the hypothalamic-pituitary system. The spontaneous ovulatory surge of gonadotrophin is produced by a positive feedback cascade. The cascade is initiated by an increase in the plasma concentration of oestradiol-17 beta which triggers a surge of luteinizing hormone releasing hormone (LHRH) and an increase in pituitary responsiveness to LHRH. The facilitatory action of oestrogen on pituitary responsiveness is reinforced by progesterone and the priming effect of LHRH. How oestrogen and progesterone exert their effects is not clear but the facilitatory effects of oestrogen take about 24 h, and the stimulation of LHRH release is produced by an indirect effect of oestradiol on neurons which are possibly opioid, dopaminergic or noradrenergic and which modulate the activity of LHRH neurons. In the rat, a spontaneous prolactin surge occurs at the same time as the spontaneous ovulatory gonadotrophin surge. The prolactin surge also appears to involve a positive feedback between the brain-pituitary system and the ovary. However, the mechanism of the prolactin surge is poorly understood mainly because the neural control of prolactin release appears to be mediated by prolactin inhibiting as well as releasing factors, and the precise role of these factors has not been established. The control of prolactin release is further complicated by the fact that oestradiol stimulates prolactin synthesis and release by a direct action on the prolactotrophes. Prolactin and gonadotrophin surges also occur simultaneously in several experimental steroid models. A theoretical model is proposed which could explain how oestrogen and progesterone trigger the simultaneous surge of LH and prolactin.     

An increase in in vivo release of LHRH and precocious puberty by posterior hypothalamic lesions in female rhesus monkeys (Macaca mulatta)

We have previously shown that a decrease in gamma-aminobutyric acid (GABA) tone and a subsequent increase in glutamatergic tone occur in association with the pubertal increase in luteinizing hormone releasing hormone (LHRH) release in primates. To further determine the causal relationship between developmental changes in GABA and glutamate levels and the pubertal increase in LHRH release, we examined monkeys with precocious puberty induced by lesions in the posterior hypothalamus (PH). Six prepubertal female rhesus monkeys (17.4 +/- 0.1 mo of age) received lesions in the PH, three prepubertal females (17.5 +/- 0.1 mo) received sham lesions, and two females received no treatments. LHRH, GABA, and glutamate levels in the stalk-median eminence before and after lesions were assessed over two 6-h periods (0600-1200 and 1800-2400) using push-pull perfusion. Monkeys with PH lesions exhibited external signs of precocious puberty, including significantly earlier menarche in PH lesion animals (18.8 +/- 0.2 mo) than in sham/controls (25.5 +/- 0.9 mo, P<0.001). Moreover, PH lesion animals had elevated LHRH levels and higher evening glutamate levels after lesions, whereas LHRH changes did not occur in sham/controls until later. Changes in GABA release were not discernible, since evening GABA levels already deceased at 18-20 mo of age in both groups and morning levels remained at the prepubertal levels. The age of first ovulation in both groups did not differ. Collectively, PH lesions may not be a good tool to investigate the mechanism of puberty, and, taking into account the recent findings on the role of kisspeptins, the mechanism of the puberty onset in primates is more complex than we initially anticipated.     

Analysis of androgen action on pituitary gonadotropin and prolactin secretion in ewes

To study the role of androgens in the control of gonadotropin and prolactin secretion in ther ewe, we have characterized androgen receptors in pituitary cytosol, and investigated the effect of androgens on pituitary hormone release in vivo and in vitro. High affinity, low capacity receptors, with an affinity for methyltrienolone (R1881) greater than 5 alpha-dihydrotestosterone (5 alpha-DHT) greater than testosterone (T) much greater than androstenedione (A4), estradiol-17 beta (E2) and progesterone (P), were identified in pituitary cytosol. Addition of 1 nM 5 alpha-DHT, but not A4, inhibited luteinizing hormone (LH) release from pituitary cells in vitro, induced by 10(10) to 10(-7) M luteinizing hormone releasing hormone (LHRH). The release of follicle-stimulating hormone (FSH) with 10(-9) M LHRH was inhibited when cells were incubated with 1 nM 5 alpha-DHT. 5 alpha-DHT had no effect when higher or lower doses of LHRH were used. In ovariectomized ewes, neither an i.v. injection of 1 mg, nor intracarotid injections of up to 1 mg, 5 alpha-DHT affected plasma LH, FSH or prolactin levels, despite dose-related increases in plasma 5 alpha-DHT levels. Daily or twice daily i.m. injections of 5 mg 5 alpha-DHT in oil did not affect LH or FSH levels, but daily injections of 20 mg significantly reduced plasma LH levels within 4 days and plasma FSH levels within 6 days. Thus, despite the presence of androgen receptors in the ewe pituitary, we conclude that androgens per se are of minimal importance in the regulation of pituitary LH, FSH and prolactin secretion in the ewe. The low binding affinity of A4 and the lack of its effect on hormone secretion in vitro suggests that A4 may act as an estrogen precursor rather than an androgenic hormone. The function of the pituitary androgen receptor remains to be established.     

A functional dimorphism in the response of the hypothalamic-pituitary axis of prepubertal rats to steroid treatment

In the present experiment we examined the circadian neural luteinizing hormone releasing hormone (LHRH) and serum luteinizing hormone (LH) response of prepubertal male and female rats under varying steroidal manipulations (Intact, Castrate, Castrate + estradiol 17 beta [E2] + oil and Castrate + E2 + progesterone[P]). Prepubertal males demonstrated greater and acyclic LHRH concentrations in both the medial basal hypothalamus (MBH) and preoptic-suprachiasmatic regions (POA-Sch) irrespective of steroid treatment. In steroid-treatment castrated male rats only the negative feedback action on serum LH levels were observed with maximal effect in animals injected with the combination E2 + P. In contrasts, prepuberal castrated females exhibited both inhibitory and stimulatory feedback actions on LH release following steroid treatment. Moreover, a distinctive, significant, progesterone-dependent increase in AM POA-Sch, but not MBH-LHRH concentrations was detected. These results demonstrate the existence of a functional sexual dimorphism in the positive feedback response of the POA-Sch-pituitary axis of prepubertal rats to progesterone treatment.     

Temporal sequence of neuroendocrine events associated with the transfer of male golden hamsters from a stimulatory to a nonstimulatory photoperiod

The transfer of male golden hamsters from long day (LD) to short day (SD) conditions results in gonadal atrophy within 8 weeks and significant reductions in LH, FSH, and prolactin (Prl) secretion as early as 4 weeks. Changes in hypothalamic neurotransmitter metabolism precede these changes in pituitary hormone secretion. Thus median eminence norepinephrine (NE) turnover declines steadily after SD exposure, although the differences as compared to turnover in LD hamsters are not significant until Week 4. Median eminence dopamine (DA) turnover is reduced significantly within 1 week. Turnover of NE and DA in the medial basal hypothalamus also changes significantly within 1 or 2 weeks of SD exposure, but the changes are not maintained through Week 8, despite continued reductions in levels of circulating LH, FSH, and Prl. Reductions in median eminence NE metabolism appear to be responsible for the decrease in LH and FSH release. Initial decreases in Prl release appear to be hypothalamic in origin, but the hypothalamic factor(s) responsible for this change is not evident. An increase in inhibitory input from tuberoinfundibular dopaminergic neurons is clearly not involved.     

A model for the control of testosterone secretion

We produce here a model to explain the control of testosterone secretion. In this model the hypothalamic secretion of the hormone LHRH (luteinizing hormone releasing hormone) is controlled by a combination of local testosterone concentration and of the local concentration of the pituitary hormone LH (luteinizing hormone). Since LHRH stimulates the release of LH, and LH in turn stimulates the release of testosterone, the three hormones constitute a three-component "feedback" network. We show how this model is able to account for the pulsatility of the release of these three hormones. Furthermore, the model is consistent with results obtained from a wide range of experimental manipulations of the system. For example, it accounts for the changes observed in hormone release patterns after castration. In particular, it follows that no "neural clock", or "neural pulse-generator", is required to force the system into pulsatile behaviour.     

Effects of estradiol on circulating levels of prolactin in female rats bearing ectopic pituitaries

The existence of local mechanisms controlling the prolactin (PRL) release from anterior pituitaries (AP) grafted to an ectopic location has been recently described. To study if these mechanisms are affected by estrogens, pituitary-grafted (GRAFT) and sham-operated (SHAM) rats were injected with a single dose of estradiol benzoate (EB), their plasma PRL levels as well as their hypothalamic and AP contents of norepinephrine (NE) and dopamine (DA) being analyzed. Administration of EB to GRAFT animals produced a small increase in their previously high plasma PRL levels, with both an increased NE and a decreased DA content in the ectopic AP. Since NE enhances the PRL release from ectopic AP and DA partially inhibits this secretion these changes may explain such a small increase in PRL levels. However, an additional increase in the decreased PRL release from the in situ AP of these animals cannot be discarded since EB produced also a decrease of the DA content in this tissue with an unaltered hypothalamic content. Finally, administration of this steroid to SHAM animals produced an important increase in plasma PRL levels. Since this increase was correlative to a decrease in DA and NE hypothalamic contents and unaltered AP contents. EB may be supposed to be able to reduce the DA synthesis in the tuberoinfundibular neurons, while the changes in noradrenergic inputs could be more related to the feedback effects of estrogens on the gonadotrophin release.     

Effects of subchronic alternating cadmium exposure on dopamine turnover and plasma levels of prolactin, GH and ACTH

This study was undertaken to analyze if the effects of subchronic alternating cadmium exposure on pituitary hormone secretion are mediated by changes in dopamine turnover in an age dependent way or are directly correlated to cadmium accumulation at the hypothalamic-pituitary axis. Male rats were treated sc. from day 30 to 60 (prepubertal period) or from day 60 to 90 (adult age) of life, with cadmium chloride (CdCl₂) at a dose of 0.5 and 1.0 mg kg^–1 bw, every 4th day in an alternate schedule, starting with the smaller dose. Dopamine (DA) turnover, expressed as the ratio of acid 3,3-dihidroxifenil acetic (DOPAC)/DA in various hypothalamic areas, the plasma levels of prolactin, growth hormone (GH) and adrenocorticotropic hormone (ACTH), and cadmium accumulation in the hypothalamus and pituitary were studied. Prepubertal cadmium exposure decreased DA content in all hypothalamic areas studied, although its turnover was not modified. A decrease in plasma ACTH levels with no changes in plasma prolactin and GH levels were found. Cadmium did not accumulate in pituitary while it increased in the hypothalamus. Metal exposure during adulthood decreased DA content in mediobasal and posterior hypothalamus, and its turnover in posterior hypothalamus and median eminence. It decreased plasma prolactin and ACTH levels but not those of GH. Cadmium concentration increased in both hypothalamus and pituitary. These results suggest that cadmium exposure produces age dependent changes on the secretory mechanisms of the pituitary hormones studied, related to the selective accumulation of the metal at both hypothalamic and hypophyseal level changes. However the effects of the metal are not mediated by dopamine.