Negative feedback as an obligatory antecedent to the estradiol-induced luteinizing hormone surge in ovariectomized pigs

In ovariectomized pigs, estradiol treatment induces a preovulatory-like luteinizing hormone (LH) surge, but only after serum LH concentrations are suppressed for 48 h. This inhibition of LH release is attributable in large part to inhibition of gonadotropin-releasing hormone (GnRH) release. The present report examines the dependency of the estradiol-induced LH surge on this preceding phase of negative feedback. Ten ovariectomized gilts were given an i.m. injection of estradiol benzoate (10 micrograms/kg BW). Beginning at the time of estradiol treatment, 5 of these gilts received 1-microgram GnRH pulses i.v. every 45 min for 48 h, i.e. during the period of negative feedback. The remaining 5 control gilts received comparable infusions of vehicle. Estradiol induced the characteristic biphasic LH response in control gilts. On the other hand, the inhibitory LH response to estradiol was prevented and the ensuing LH surge was blocked in 4 of the 5 gilts given GnRH pulses during the negative feedback phase. These results indicate that suppressing release of GnRH and/or LH is an important antecedent to full expression of the LH surge in ovariectomized pigs. Assimilation of this observation with the existing literature provides novel insights into the neuroendocrine control of LH secretion in castrated and ovary-intact gilts.     

Gonadotropin and prolactin secretion following intraventricular administration of morphine in gilts

The effects of central nervous system administration of morphine on secretion of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were investigated in ovariectomized gilts stereotaxically implanted with lateral ventricular cannulas. In Experiment 1, mean serum LH and follicle-stimulating hormone concentrations and serum LH pulse frequency were unaffected by artificial cerebrospinal fluid administration (P greater than 0.1), but decreased (P less than 0.01) in 8 of 11 gilts when 500 micrograms of morphine were given 3 hr later. Serum LH pulse amplitude was unaffected (P greater than 0.1) by cerebrospinal fluid or morphine injection. In Experiment 2, luteinizing hormone concentrations decreased (P less than 0.0001) and prolactin concentrations increased (P less than 0.0001), but follicle-stimulating hormone concentrations did not change (P greater than 0.1) after 500 micrograms of morphine. Gonadotropin responses to 10 micrograms of gonadotropin-releasing hormone, given 2 hr after intraventricular injection, were similar (P greater than 0.1) for morphine- and cerebrospinal fluid-treated gilts. These results indicate that morphine inhibits LH secretion at the level of the central nervous system, and are consistent with the concept that endogenous opioid peptides participate in the regulation of gonadotropin and prolactin release in pigs.     

Modulation of luteinizing hormone pulse amplitude by the frequency of luteinizing hormone-releasing hormone stimulation and by testosterone in castrated, hypothalamic-lesioned male rats

The frequency of spontaneous luteinizing hormone (LH) pulses is thought to be a direct result of the frequency of luteinizing hormone-releasing hormone (LHRH) pulses from the hypothalamus. By contrast, the amplitude of spontaneous LH pulses may be controlled by several factors other than the amplitude of LHRH pulses. We tested two hypotheses: 1) that LH pulse amplitude is determined in part by the frequency of LHRH pulses of constant magnitude, and 2) that testosterone (T) exerts a direct feedback effect on the pituitary gland to regulate LH pulse amplitude. Gonadal feedback was eliminated by castrating adult male rats (n = 20). Endogenous LHRH secretion was eliminated by lesioning the medial basal hypothalamus. Serum LH levels (0.19 +/- 0.04 ng/ml RP-2, mean +/- SEM) and T levels (0.15 +/- 0.02 ng/ml), measured several weeks after hypothalamic lesioning, confirmed the hypogonadotropic hypogonadal state of the animals. During a 8-h period, unanesthetized, unrestrained animals were injected with 40-ng pulses of LHRH via catheters into the jugular vein, and blood samples for LH measurement were drawn at 10-min intervals. The LHRH pulse interval was 20 min during the first 4 h in all animals. The pulse interval was doubled to 40 min in half of the animals (n = 10) during the next 4 hours; in the other 10 animals, the pulse interval was maintained constant at 20 min throughout the study. Within both of these groups, one-half of the animals (n = 5) were infused with T to achieve a physiological level of T in serum (2.46 +/- 0.36 ng/ml at 4 h), while the other half received vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Luteinizing hormone secretion as affected by hypophyseal stalk transection and estradiol-17beta in ovariectomized gilts

The objectives were to determine hypothalamic regulation of pulsatile luteinizing hormone (LH) secretion in female pigs and the biphasic feedback actions of estradiol-17beta (E(2)-17beta). In the first study, the minimum effective dosage of E(2)-17beta that would induce estrus in ovariectomized gilts was determined to be 20microg/kg body weight. In the second study, ovariectomized gilts were assigned randomly on day 0 to treatments: (a) hypophyseal stalk transection (HST), (b) cranial sham-operated control (SOC), and (c) unoperated control (UOC). On day 3, gilts from each group received a single i.m. injection of either E(2)-17beta (20microg/kg body weight) or sesame oil. Blood was collected from an indwelling jugular cannula at 15min intervals for 3h before (day -2) and after treatment (day 2) from HST, SOC and UOC gilts. On day 3, blood was collected at 2h intervals for 12h after E(2)-17beta or sesame oil injection and at 4h intervals thereafter for 108h. Pulsatile LH secretion in all gilts 2 days after ovariectomy exhibited a frequency of 0.9+/-0.06peaks/h, amplitude of 1.3+/-0.13ng/ml, baseline of 0.8+/-0.07. Serum LH concentrations from SOC and UOC gilts were similar on day 2 and profiles did not differ from those on day -2. In HST gilts pulsatile LH release was abolished and mean LH concentration decreased compared with controls (0 versus 0.9+/-0. 06peaks/h and 0.77+/-0.03 versus 1.07+/-0.07ng/ml, respectively; P<0. 05). E(2)-17beta or sesame oil did not affect serum LH concentration in HST gilts, and LH remained constant throughout 120h (0.7+/-0. 07ng/ml). In SOC and UOC control gilts, E(2)-17beta induced a 60% decrease (P<0.05) in LH concentration within 12h, and LH remained low until 48h, then increased to peak values (P<0.05) by 72h, followed by a gradual decline to 120h. Although pituitary weight decreased 31% in HST gilts compared with controls (228 versus 332mg, P<0.05), an abundance of normal basophils was evident in coronal sections of the adenohypophysis of HST comparable to that seen in control gilts. The third and fourth studies determined that hourly i. v. infusions of LHRH (2microg) and a second injection of E(2)-17beta 48h after the first had no effect on the positive feedback action of estrogen in UOC. However, in HST gilts that received LHRH hourly, the first injection of E(2)-17beta decreased (P<0.05) plasma LH concentrations while the second injection of E(2)-17beta failed to induce a positive response to estrogen. These results indicate that both pulsatile LH secretion and the biphasic feedback action of E(2)-17beta on LH secretion depend on hypothalamic regulatory mechanisms in the gilts. The isolated pituitary of HST gilts is capable of autonomous secretion of LH; E(2)-17beta will elicit direct negative feedback action on the isolated pituitary gland if the gonadotropes are supported by exogenous LHRH, but E(2)-17beta at high concentrations will not induce positive feedback in isolated pituitaries. Thus, the direct effect of E(2)-17beta on the pituitary of monkeys cannot be mimicked in pigs.     

Estrogen and leptin have differential effects on FSH and LH release in female rats

Prior experiments have shown that the adipocyte hormone leptin can advance puberty in mice. We hypothesized that it would also stimulate gonadotrophin secretion in adults. Since the secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is drastically affected by estrogen, we hypothesized that leptin might have different actions dependent on the dose of estrogen. Consequently in these experiments, we tested the effect of injection of leptin into the third cerebral ventricle of ovariectomized animals injected with either the oil diluent, 10 microg or 50 microg of estradiol benzoate 72 hr prior to the experiment. The animals were ovariectomized 3-4 weeks prior to implantation of a cannula into the third ventricle 1 week before the experiments. The day after implantation of an external jugular catheter, blood samples (0. 3 ml) were collected just before and every 10 min for 2 hr after 3V injection of 5 microl of diluent or 10 microg of leptin. Both doses of estradiol benzoate equally decreased plasma LH concentrations and pulse amplitude, but there was a graded decrease in pulse frequency. In contrast, only the 50-microg dose of estradiol benzoate significantly decreased mean plasma FSH concentrations without significantly changing other parameters of FSH release. The number of LH pulses alone and pulses of both hormones together decreased as the dose of estrogen was increased, whereas the number of pulses of FSH alone significantly increased with the higher dose of estradiol benzoate, demonstrating differential control of LH and FSH secretion by estrogen, consistent with alterations in release of luteinizing hormone releasing hormone (LHRH) and the putative FSH-releasing factor (FSHRF), respectively. The effects of intraventricularly injected leptin were drastically altered by increasing doses of estradiol benzoate. There was no significant effect of intraventricular injection of leptin (10 microg) on the various parameters of either FSH or LH secretion in ovariectomized, oil-injected rats, whereas in those injected with 10 microg of estradiol benzoate there was an increase in the first hr in mean plasma concentration, area under the curve, pulse amplitude, and maximum increase of LH above the starting value (Deltamax) on comparison with the results in the diluent-injected animals in which there was no alteration of these parameters during the 2 hr following injection. The pattern of FSH release was opposite to that of LH and had a different time-course. In the diluent-injected animals, probably because of the stress of injection and frequent blood sampling, there was an initial significant decline in plasma FSH at 20 min after injection, followed by a progressive increase with a significant elevation above the control values at 110 and 120 min. In the leptin-injected animals, mean plasma FSH was nearly constant during the entire experiment, coupled with a significant decrease below values in diluent-injected rats, beginning at 30 min after injection and progressing to a maximal difference at 120 min. Area under the curve, pulse amplitude, and Deltamax of FSH was also decreased in the second hour compared to values in diluent-injected rats. In contrast to the stimulatory effects of intraventricular injection of leptin on pulsatile LH release manifest during the first hour after injection, there was a diametrically opposite, delayed significant decrease in pulsatile FSH release. This differential effect of leptin on FSH and LH release was consistent with differential effects of leptin on LHRH and FSHRF release. Finally, the higher dose of E2 (50 microg) suppressed release of both FSH and LH, but there was little effect of leptin under these conditions, the only effect being a slight (P < 0.04) increase in pulse amplitude of LH in this group of rats. The results indicate that the central effects of leptin on gonadotropin release are strongly dependent on plasma estradiol levels. These effects are consistent w     

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.     

Luteinizing hormone secretion in hypophysial stalk-transected pigs given progesterone and pulsatile gonadotropin-releasing hormone

This study was conducted to determine whether progesterone inhibits luteinizing hormone (LH) secretion in female pigs by a direct action on the pituitary gland. Eight ovariectomized, hypophysial stalk-transected gilts were given 1-microgram pulses of gonadotropin-releasing hormone iv every 45 min from Day 0 to 12. On Days 5-12, each of four gilts received either progesterone or oil vehicle im at 12-hr intervals. Serum progesterone concentrations in steroid-treated gilts reached 70 +/- 6.8 ng/ml (mean +/- SE) by Day 8 and remained elevated thereafter, whereas serum progesterone concentrations in oil-treated controls were less than 1 ng/ml for the entire study. Daily serum LH concentrations were not different between gilts treated with progesterone or oil. The 1-microgram pulses of gonadotropin-releasing hormone reliably evoked pulses of LH in both treatment groups. The LH pulse frequency and amplitude, assessed from samples collected every 15 min for 6 hr on Day 12, were similar for progesterone- and oil-treated gilts. These results provide evidence that progesterone does not act at the pituitary gland to alter LH secretion in pigs.     

Hypothalamic deafferentation and luteinizing hormone-releasing hormone effects on secretion of luteinizing hormone in prepubertal pigs

The control of luteinizing hormone (LH) secretion was investigated in ovariectomized, prepubertal Yorkshire pigs by comparing the effects of anterior (AHD), complete (CHD), and posterior (PHD) hypothalamic deafferentation to sham-operated controls (SOC). Gilts (n = 16) were assigned randomly to treatments, fitted with an indwelling jugular catheter, and ovariectomized 2 days before deafferentation or sham-operation (Day 0). Blood for radioimmunoassay (RIA) of LH was collected sequentially at 20-min intervals for a period of 2 h before and 24, 48, 72, and 96 h after hypothalamic deafferentation or SOC. Episodic LH release after AHD or CHD was abolished (p less than 0.01), but not after PHD or SOC. Concentrations of serum LH in AHD and CHD dropped (p less than 0.01) at 24 and 48 h after surgery. Levels of LH before and after surgery in PHD and SOC were similar (p greater than 0.05). Infusion of 25 micrograms LH-releasing hormone (LHRH) i.v. at 72 and 96 h after hypothalamic deafferentation and SOC increased (p less than 0.01) serum LH to peak levels within 15 min. after infusion; LH returned to basal levels 60-80 min later. By 96 h after surgery, LH response to LH-releasing hormone (LHRH) was less in AHD and CHD as compared with the response at 72 h postinjection. Concentrations of LH in PHD and SOC were similar (p greater than 0.05) at 72 and 96 h, respectively. The results from this study clearly indicate that neural stimuli originating or traversing the neural areas rostral to the median eminence are required for secretion of LH in the pig.(ABSTRACT TRUNCATED AT 250 WORDS)     

Opioidergic control of luteinizing hormone release in the female rabbit: influence of ovariectomy and steroid replacement on pulsatile secretion

The influence of ovariectomy and steroid replacement on naloxone-induced changes in pulsatile secretion of luteinizing hormone (LH) in the female rabbit was examined. Blood samples were taken every 5 min through an indwelling catheter in the rabbit ear artery, and plasma was stored until assayed for LH by established radioimmunoassay procedures. In the intact animal, saline injection had no effect on LH secretion. Although naloxone (10 mg/kg) caused a 7-fold increase in mean LH pulse amplitude by 30 min after injection, this increase was not statistically significant because 5 of 11 animals did not respond. In animals ovariectomized 48 h previously, naloxone significantly increased LH concentration by 194% at 23 min after injection. When long-term ovariectomized rabbits were treated with estradiol benzoate and then were given naloxone, no significant increase in LH was observed, although many animals did respond. Treatment of long-term ovariectomized rabbits with 1 microgram estradiol benzoate and 100 micrograms progesterone or 1 mg testosterone propionate on Days 1 and 3 and naloxone on Day 4 resulted in a significant increase in LH 19-24 min later. Although there was an increase in pulse amplitude, no change was detected in pulse frequency after naloxone. These data suggest that the hypothesis of steroid-opioid coupling in the control of LH secretion is not applicable to the female rabbit.     

Effects of an opioid antagonist on pulsatile luteinizing hormone secretion in the ewe vary with changes in steroid negative feedback

In ewes during the breeding season, estradiol (E) and progesterone (P) synergistically regulate pulsatile luteinizing hormone (LH) secretion. E primarily inhibits LH pulse amplitude and P inhibits LH pulse frequency. To determine if endogenous opioid peptides (EOP) mediate these negative feedback effects, we administered the long-acting opioid antagonist WIN 44,441-3 (WIN) to intact ewes during the luteal and follicular phases of the estrous cycle and to ovariectomized ewes treated with no steroids, E, P, or E plus P. Steroid levels were maintained at levels seen during the estrous cycle by Silastic implants placed shortly after surgery. WIN increased LH pulse frequency, but not amplitude, in luteal phase ewes. In contrast, during the follicular phase, LH pulse amplitude was increased by WIN and pulse frequency was unchanged. Neither LH pulse frequency nor pulse amplitude was affected by WIN in long-term ovariectomized ewes untreated with steroids. In contrast, WIN slightly increased LH pulse frequency in short-term ovariectomized ewes. WIN also increased LH pulse frequency in ovariectomized ewes treated with P or E plus P. WIN did not affect pulse frequency but did increase LH pulse amplitude in E-treated ewes. These results support the hypothesis that EOP participate in the negative feedback effects of E and P on pulsatile LH secretion during the breeding season and that the inhibitory effects of EOP may persist for some time after ovariectomy.     

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.     

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.     

Effects of intraventricular norepinephrine on LH release in short- and long-term ovariectomized steroids-primed rats

This study examined the noradrenergic mechanism in regulation of luteinizing hormone (LH) release in short- and long-term ovariectomized (OVX) steroids-primed rats. All rats were OVX on the diestrous day 1(D1) morning about 1000 h. After OVX, rats in the short-term OVX group were immediately primed with estradiol (E2, 0.1 mg/kg BW s.c.), fitted with atrial Silastic tubing, and a guide cannula in the right lateral cerebroventricle stereotaxically. Rats in the long-term OVX group received the same treatment (E2, atrial tubing and guide cannula implantation) three weeks later. Rats in both groups received progesterone (2 mg/rat s.c.) at 0930 h on the next day after E2. At 1000 h, intraventricular administration of norepinephrine HCl (NE, 0.01, 0.1, or 1.0 microgram in 2 microliters saline) was given. In short-term OVX-steroids-primed rats, NE did not alter LH levels in the peripheral plasma within 60 or 100 min. By contrast, in long-term OVX-steroids-primed rats, 1.0 microgram of NE gradually decreased plasma LH concentrations, which became significantly different from the initial value at the 60 min time point after treatment. On the other hand, intraventricular injection of 5 ng of the LH-releasing hormone (LHRH) elevated plasma LH concentrations within 10 min in both groups of rats, but at different efficacy: a brief release of LH in short-term OVX-steroids-primed rats and a prolonged release of LH in long-term OVX-steroids-primed rats. These results indicated that the interval after OVX plays a critical role in modulating the responsiveness to NE and LHRH in the steroids-primed OVX rats.     

Effect of alterations in pulsatile luteinizing hormone release on ovarian follicular atresia and steroid secretion on diestrus 1 in the rat estrous cycle

This study examined the importance of pulsatile luteinizing hormone (LH) release on diestrus 1 (D1; metestrus) in the rat estrous cycle to ovarian follicular development and estradiol (E2) secretion. Single injections of a luteinizing hormone-releasing hormone (LHRH) antagonist given at -7.5 h prior to the onset of a 3-h blood sampling period on D1 reduced mean blood LH levels by decreasing LH pulse amplitude, while frequency was not altered. Sequential injections at -7.5 and -3.5 h completely eliminated pulsatile LH secretion. Neither treatment altered the total number of follicles/ovary greater than 150 mu in diameter, the number of follicles in any size group between 150 and 551 mu, or plasma E2, progesterone, or follicle-stimulating hormone (FSH) levels. However, both treatments with LHRH antagonist significantly increased the percentage of atretic follicles in the ovary. These data indicate that: 1) pulsatile LH release is an important factor in determining the rate at which follicles undergo atresia on D1; 2) reductions in LH pulse amplitude alone are sufficient to increase the rate of follicular atresia on D1; 3) an absence of pulsatile LH release for a period of up to 10 h on D1 is not sufficient to produce a decline in ovarian E2 secretion, most likely because the atretic process was in its early stages and had not yet affected a sufficient number of E2-secreting granulosa cells to reduce the follicle's capacity to secrete E2; and 4) suppression or elimination of pulsatile LH release on D1 is not associated with diminished FSH secretion.     

Effect of bombesin on basal and stimulated secretion of some pituitary hormones in humans

The effect of bombesin (5 ng/kg/min X 2.5 h) on basal pituitary secretion as well as on the response to thyrotropin releasing hormone (TRH; 200 micrograms) plus luteinizing hormone releasing hormone (LHRH; 100 micrograms) was studied in healthy male volunteers. The peptide did not change the basal level of growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). On the contrary, the pituitary response to releasing hormones was modified by bombesin administration. When compared with control (saline) values, prolactin and TSH levels after TRH were lower during bombesin infusion, whereas LH and FSH levels after LHRH were higher. Thus bombesin affects in man, as in experimental animals, the secretion of some pituitary hormones.     

Increased suppression of luteinizing hormone secretion by chronic and acute estradiol administration in underfed adult female rats

These studies attempted to elucidate the relationship between estradiol and luteinizing hormone (LH) secretion in chronically underfed (R) adult female rats. Examination of the response to ovariectomy revealed a significant delay in the onset of the postcastration increase in LH secretion in R females compared to control (C) animals. Chronic estrogen treatment in the form of Silastic capsules containing varying doses of E2. The response of C females was dose-dependent, ranging from complete suppression at 10 micrograms E2/animal to an absence of inhibition at 2.4 micrograms E2/animal. The acute response of LH secretion to E2 administration in the ovariectomized female indicated an increased suppression of plasma LH at 6 and 24 h after a single s.c. injection of estradiol benzoate (EB) in R compared to C animals. There was no difference between R and C rats in the ratio of free to protein-bound estradiol in the serum. The results of these studies suggest that the negative feedback efficacy of estrogen on LH secretion is significantly enhanced by reduced food intake in adult female rats and may be responsible for the loss of reproductive cyclicity in these animals.     

Simultaneous measurement of luteinizing hormone-releasing hormone and luteinizing hormone during estradiol-induced luteinizing hormone surges in the ovariectomized ewe

Sequential bleeding and push-pull perfusion of the hypothalamus were used to characterize luteinizing hormone (LH) and LH-releasing hormone (LHRH) release in ovariectomized (OVX) ewes after injection of corn oil or estradiol benzoate (EB). Push-pull cannulae were surgically implanted into the stalk median eminences of 24 OVX ewes. Seven to 14 days later each of 20 animals was given an i.m. injection of 50 micrograms EB. Blood samples and push-pull perfusate were collected at 10-min intervals for 6-12 h beginning 12-15 h after EB injection. Four OVX ewes were given i.m. injections of corn oil 7 days after implantation of push-pull cannulae. Blood samples and push-pull perfusate were collected at 10-min intervals for 4 h between 18 and 22 h after injection of corn oil. Luteinizing hormone remained below 2 ng/ml throughout most of the sampling periods in 9 of 20 EB-treated ewes. In 5 of these 9 LHRH also was undetectable, whereas in 4 LHRH was detectable (1.84 +/- 0.29 pg/10 min), but did not increase with time. Preovulatory-like surges of LH occurred in 11 EB-treated ewes, but LHRH was undetectable in 5. In 4 of 6 ewes showing LH surges and detectable LHRH, sampling occurred during the onset of the LH surge.(ABSTRACT TRUNCATED AT 250 WORDS)     

The response of the anterior pituitary and testes to synthetic luteinizing hormone-releasing hormone (LHRH) and the effect of castration on pituitary responsiveness in the maturing chicken fed aflatoxin

The responsiveness of the anterior pituitary to exogenous luteinizing hormone-releasing hormone (LHRH; 20 micrograms/kg body weight) and the subsequent stimulation of testosterone secretion by the testes was studied after administration of dietary aflatoxin (10 ppm) to 9-wk-old male chickens. In both control and aflatoxin-treated males, there were significant (p less than 0.05) increases in plasma luteinizing hormone (LH) concentrations following LHRH administration, which peaked at 5 min post injection and declined thereafter. Plasma testosterone levels increased soon after the LHRH injection in control males, secondary to elevated LH levels in the peripheral circulation, and continued to increase throughout the experimental period. In contrast, this LH-induced elevation in plasma testosterone was delayed in aflatoxin-treated males, with no substantial increase until 20 min post-LHRH injection. In a subsequent experiment, castration of aflatoxin-fed males resulted in an altered response to exogenous LHRH, as compared to their intact counterparts. Based on these data, it appeared that while the LH-secretory capacity of the anterior pituitary was not diminished in birds receiving aflatoxin, the testicular response to exogenous LHRH was altered during aflatoxicosis. Additionally, the effect of castration on plasma LH profiles after LHRH administration provides preliminary evidence for extra-testicular effects of dietary aflatoxin on reproduction in the avian male.     

Presence of positive feedback in males with Klinefelter's syndrome

This study examined the effect of 17 beta-estradiol (E2) on basal and luteinizing hormone (LH)-releasing hormone (LHRH)-stimulated gonadotropin secretion in 9 patients with Klinefelter's syndrome. Intramuscular injection of E2 (10 micrograms/kg/day during 5 days) induced a rapid decrease in follicle-stimulating hormone (FSH) and LH levels. The maximum suppression was observed on day 7 (D7) for FSH [median 9.7 mIU/ml (range 4.6-37.8) vs. 21.7 mIU/ml (range 12.2-56.9)] and on D2 for LH [median 13.6 mIU/ml (range 6.8-25.2) vs. 21.2 mIU/ml (range 13-54.7)]. E2 concentrations rose and reached their peak values on D3 [median 723 pmol/l (range 517-1,247.8) vs. 110.1 pmol/l (range 68.6-227.5) on D0]. These changes were followed by a subsequent rise in LH on D4 [36.7 mIU/ml (range 19.4-77.7)]. LH response to LHRH was higher during E2 treatment: median value of absolute peaks: 156.3 mIU/ml (range 56.7-188.6) on D4 vs. 64 mIU/ml (range 38.9-131) on DO. These results demonstrate the presence of a positive feedback in patients with Klinefelter's syndrome.     

Effect of luteinizing hormone releasing hormone pulse characteristics on comparative luteinizing hormone and follicle stimulating hormone secretion from superfused rat anterior pituitary cell cultures

We have shown that 4 ng luteinizing hormone releasing hormone (LHRH) pulses induced significantly greater luteinizing hormone (LH) release from proestrous rat superfused anterior pituitary cells with no cycle related differences in follicle stimulating hormone (FSH). Current studies gave 8 ng LHRH in various pulse regimens to study amplitude, duration and frequency effects on LH and FSH secretion from estrous 0800, proestrous 1500 and proestrous 1900 cells. Regimen 1 gave 8 ng LHRH as a single bolus once/h; regimen 2 divided the 8 ng into 3 equal 'minipulses' given at 4 min intervals to extend duration; regimen 3 gave the 3 'minipulses' at 10 min intervals, thereby further extending duration: regimen 4 was the same as regimen 2, except that the 3 'minipulses' were given at a pulse frequency of 2 h rather than 1 h. In experiment 1, all four regimens were employed at proestrus 1900. FSH was significantly elevated by all 8 ng regimens as compared to 4 ng pulses; further, 8 ng divided into 3 equal 'minipulses' separated by 4 min at 1 and 3 h frequencies (regimens 2 and 4) resulted in FSH secretion that was significantly greater than with either a single 8 ng bolus (regimen 1) or when the 'minipulses' were separated by 10 min (regimen 3). In experiment 2, at proestrus 1500, FSH response to the second pulse of regimen 4 was significantly greater than in regimen 2; LH release was significantly suppressed at pulse 2 compared to regimen 2 accentuating divergent FSH secretion. At estrus 0800, FSH response to the second pulse of regimen 4 was significantly stimulated FSH at proestrus 1900, 1500 and estrus 0800, FSH divergence was most marked at proestrus 1500. These data indicate a potential role for hypothalamic LHRH secretory pattern in inducing divergent gonadotropin secretion in the rat.