Luteinizing Hormone-releasing Hormone Infusion Research Articles

Pituitary and testicular response to luteinizing hormone releasing hormone in normal and sulpiride-induced hyperprolactinaemic men.

Pituitary and testicular response to an intravenous infusion of 480 micrograms luteinizing hormone releasing hormone (LHRH) for 8 hours (1 microgram/min) was investigated in 8 male volunteers in normal and hyperprolactinaemic state. Eight normal men were given 150 mg of sulpiride daily for 14 days. Serum prolactin (PRL) levels were elevated significantly, but basal serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) did not change following daily oral administration of sulpiride in 8 normal men. Eight men showed biphasic LH response to LHRH infusion in both normal and hyperprolactinaemic state, and there was a rather exaggerated response in serum LH concentration in hyperprolactinaemic state. Serum FSH response to LHRH was similar in normal and hyperprolactinaemic state. Although slight increase in serum testosterone concentration was observed during LHRH infusion in normal and hyperprolactinaemic state, the statistical difference was not significant. The result of the present study suggests that the function of the hypothalamic-pituitary-testicular axis, as measured by serum gonadotrophin and testosterone responses, is well reserved.

Clinical evaluation of the luteinizing hormone-releasing hormone (LH-RH) test in cases with anatomically verified disorders of the hypothalamo-pituitary region.

The effect of slow intravenous infusion of luteinizing hormone-releasing hormone (LH-RH) on serum LH was studied in 58 patients with anatomically verified hypothalamo-pituitary disorders as well as in control groups. Normal responses to the LH-RH test were found in 15 out of 15 cases with intrasellar pituitary tumours and in five out of six cases after transsphenoidal surgery for an intrasellar pituitary tumour. Twenty-one out of 25 patients where a pituitary tumour with both supra- and intrasellar extension had been removed had pathological responses to the test. All eight patients with hypothalamic disorders, mainly tumours not directly influencing the pituitary, gave normal responses to the LH-RH tests. Out of four patients with hypothalamopituitary malformations a pathological response to the LH-RH infusion was found in three cases and a normal response in one case. The increase of serum LH after LH-RH infusion was pronounced and rather constant in males and post-menopausal women. It was more difficult to evaluate a “normal” test response in women of fertile ages because of the great variations during the different menstrual phases. It is concluded that the LH-RH test may be of importance in the investigation of patients with suspected tumours of the pituitary as well as for differential diagnosis between hypothalamic and pituitary disorders of gonadotropin secretion.

Effect of naloxone and pulsatile luteinizing-hormone-releasing hormone infusions on oestradiol-induced luteinizing hormone surges in immature gilts

The aim of the study was to understand why immature 60-day-old gilts produce delayed low amplitude luteinizing hormone (LH) surges in response to oestradiol benzoate. In Expt 1, gilts (n = 36) were challenged with oestradiol benzoate and subsequently received either no further treatment or were infused with saline or various doses of the opioid antagonist, naloxone, for 6-48 h during the expected LH surge (48-96 h after oestradiol benzoate). No differences were observed among groups in the magnitude or duration of the LH surge. In contrast to the other groups, LH concentrations in gilts infused for 48 h with naloxone did not decrease after the surge period. In Expt 2, gilts (n = 34) were challenged with oestradiol benzoate or sesame oil and subsequently received pulses of luteinizing-hormone-releasing hormone (LHRH) or saline solution during the expected surge period. Two other groups were fed methallibure to pharmacologically suppress the oestradiol benzoate-induced LH surge. In addition, one of these groups was given pulses of an LHRH agonist (LHRH-A) during the surge period. Within 2 h of the start of pulsatile LHRH infusion, LH increased in sesame oil-treated gilts, but not in oestradiol benzoate-treated gilts, suggesting that the pituitary responsiveness to LHRH in immature gilts is decreased by oestrogen before the onset of the LH surge. Pulsatile LHRH infusion did not enhance the amplitude of oestradiol benzoate-induced LH surges nor did it advance its onset. Feeding methallibure suppressed the oestradiol benzoate-induced LH surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of luteinizing hormone-releasing hormone antagonistic activity in vitro.

Antagonistic analogues of luteinizing hormone-releasing hormone (LHRH) belong to a class of compounds that can be utilized for treatment of some hormone-dependent cancers and gynecologic disorders. Recently, we synthesized and tested a large number of LHRH analogues for LHRH antagonistic activity in the dispersed pituitary cell superfusion system. This fast, reliable, and dynamic system made it possible for us not only to evaluate the relative amounts of an analogue required for suppression of the LH-releasing activity of exogenous LHRH but also provided quantitative data on dynamic interactions between the LHRH analogue, LHRH receptors, and LH secretion. Three experimental paradigms were used: (i) LHRH responses after preincubation with the antagonist, (ii) pulsatile, simultaneous infusion of LHRH and the antagonistic analogue, and (iii) effects of the analogues on ongoing, continuous LH secretion induced by prolonged stimulation with LHRH. From the data obtained, we conclude that (i) the suppression of the LHRH-induced LH release was more effective and longer lasting when the cells were preincubated with the antagonistic analogues before the LHRH stimulation than in the case of simultaneous exposure; (ii) not only the potency but also the time of onset and the duration of the LH release-suppressing activity varied according to the different peptides used, resulting in different shapes of response curves; and (iii) from the accurate data obtained in this dynamic system, quantitative parameters of the in vivo interactions between the antagonists and LHRH on the LHRH receptor can be calculated.

Intratesticular Control Of Steroidogenesis

Men are men because of testosterone, and the effects of this hormone are evident in virtually every organ or tissue in a normal adult man. Because testosterone is a classical endocrine hormone with effects throughout the body, many endocrinologists will have failed to realize that, in terms of its effects on fertility, the primary role of testosterone is not endocrine but paracrine, as it is the local action of testosterone on spermatogenesis which determines fertility. When looked at from this perspective it is logical to question the traditional endocrine teaching which states that testosterone secretion is controlled solely by pituitary luteinizing hormone (LH). Certainly, the levels of testosterone and LH in peripheral blood show a close relationship, but it is not the level of testosterone in peripheral blood which determines fertility. If the primary role of testosterone is within the testis, then it is not unreasonable to expect that local mechanisms may exist to regulate the intratesticular levels of this steroid. The object of this review is to examinecritically the evidence for such mechanisms, their possible nature and their physiological and clinical significance (if any). Before reviewing the data on intratesticular control of steroidogenesis it is essential to place it in perspective. To do this, three principal questions need to be answered: (I) Why might intratesticular mechanisms for local control of testosterone production be required? (2) What is the role (or roles) of testosterone within the testis? A proper understanding of how testosterone controls spermatogenesis is essential if the local regulation of testosterone production is to be evaluated from a physiological perspective. (3) What are the constraints or problems relating to studies on the intratesticular control of steroidogenesis? It is essential to understand the potential limitations of studies on this subject so that a reasoned interpretation of the results can be made. Most relevant data is derived from studies in uitro, and the relationship of such data to the situation in uivo is often difficult to establish.

Differential Effects of an Luteinizing-Hormone-Releasing Hormone (LHRH) Antagonist Analogue on Lordosis Behavior Induced by LHRH and the LHRH Fragment Ac-LHRH<sup>5–1</sup>⁰

Both the luteinizing-hormone-releasing hormone (LHRH) decapeptide and an LHRH fragment consisting of the last 6 amino acids of the decapeptide, Ac-LHRH, have been shown to enhance lordosis behavior in ovariectomized, estradiol-benzoate treated female rats. Although the behavioral efficacy of the 2 peptides is similar, several lines of research suggest that the fragment and the decapeptide may act via different mechanisms. The present study attempted to differentiate the behavioral action of the 2 peptides by administering a long-acting LHRH antagonist analogue prior to infusion of either Ac-LHRH or LHRH. Without antagonist administration, the decapeptide and the fragment were equally effective in elevating lordotic posturing 90 min after bilateral infusion through cannulae positioned in the ventromedial nucleus of the hypothalamus (VMH). Infusion of a potent LHRH antagonist analogue [Ac-dehydro, Pro, pCl, D-Phe, DTrp]-LHRH, into the VMH significantly reduced the lordosis-to-mount ratio in animals subsequently treated with the LHRH decapeptide, but had no significant effect on lordotic behavior when the animals were subsequently infused with the Ac-LHRH fragment. The results indicate that LHRH enhancement of mating behavior is a receptor-mediated event and suggest that the Ac-LHRH fragment enhances lordotic behavior via a mechanism that is distinct from that of the LHRH decapeptide.

Effect of 5α-dihydrotestosterone and flutamide on the facilitation of lordosis by LHRH and naloxone in estrogen-primed female rats

Although 5α-dihydrotestosterone (DHT) is a potent inhibitor of lordosis behavior in ovariectomized estrogen-primed female rats, the mechanism(s) by which this steroid has this action is unknown. The present experiments sought to determine whether DHT inhibits lordosis by preventing the known facilitatory actions of luteinizing hormone-releasing hormone (LHRH), naloxone, and Substance P on lordosis. Lordosis behavior was examined in ovariectomized, estrogen-primed rats prior to or 30, 60, 90, and 180 min following intracerebroventricular (ICV) infusion of LHRH (500ng), naloxone (1 μg), Substance P (1 μg), or saline and 0.01 N acetic saline vehicles, and the effects of DHT (2.5 mg/rat) following similar treatment were examined. In Experiment 1, LHRH and naloxone increased lordosis within 30 min after infusion, while Substance P and the saline or acetic saline vehicles had no effect. Treatment with DHT in combination with estrogen prevented the facilitation of lordosis by LHRH and naloxone. In Experiment 2, ovariectomized, estrogen-primed females shown to be responsive to LHRH during a first screening test were tested for lordosis after receiving either DHT or DHT in combination with the androgen receptor antagonist, Flutamide (7.5 mg/injection × 3). Again, DHT prevented the facilitatory action of LHRH; however, Flutamide did not counteract that effect. In Experiment 3, Flutamide did not counteract the inhibitory effect of DHT on estrogen and progesterone-induced lordosis. These results demonstrate that the inhibitory effect of DHT cannot be overridden by neuroactive peptides which themselves stimulate receptivity. It seems unlikely that DHT inhibits lordosis either by interfering with the behavioral action of these peptides or by activation of the androgen receptor.

Prolactin Response to TRH Is Unaltered by Pulsatile Infusion of LHRH

Eleven boys with constitutional delay of puberty and 7 patients with hypogonadotrophic hypogonadism underwent standard thyrotrophin-releasing hormone (TRH) tests prior to and following 6 days' pulsatile infusion of luteinizing hormone-releasing hormone (240 ng/kg/pulse). There were no significant differences in basal, peak or incremental prolactin responses to TRH between the 2 groups of patients and there were no differences in the magnitude of prolactin response to TRH in either group of patients during pulsatile therapy when compared with preinfusion responses.

Immunoreactive 7B2 Concentrations in Plasma and Cerebrospinal Fluid in Pathophysiological Conditions and the Responses to Oral Glucose Load, Intravenous LH-RH, TRH and Arginine Infusion

The peptide, 7B2, originally isolated from pituitary, has been shown to be present in endocrine tumors of high concentrations in pancreatic islet tumors. Plasma from most of these patients showed very high 7B2 immunoreactivity (IR-7B2) though there is a lack of knowledge concerning physiological and pathological changes in plasma IR-7B2 levels in other conditions. To assess whether or not there is any alteration in circulating IR-7B2 levels due to age, sex or any specific condition, plasma levels of IR-7B2 were measured in the fasting state in 106 healthy subjects aged 3 months to 91 years, 101 diabetics, 28 patients with hyperthyroidism. 7 patients with primary hypothyroidism, 13 patients with liver cirrhosis, 43 patients with chronic renal failure, 35 patients with cerebral vascular accident, and 26 pregnant subjects. Twenty-four cord bloods were also included. The responses of circulating IR-7B2 to oral glucose, intravenous arginine infusion, volus thyrotropin (TRH) or volus luteinizing hormone-releasing hormone (LH-RH) injection were also evaluated. Particularly high IR-7B2 levels were found to exist in cord blood. Postnatally the concentrations decreased gradually with age to adult values (15.6 +/- 2.9pmol/liter (mean +/- SE) in 20's-60's), though plasma IR-7B2 levels again increased significantly in over 70's (37.1 +/- 3.2pmol/liter; P less than 0.01). There was no significant difference in plasma 7B2 levels in either sex. Among the pathological conditions studied, significantly high IR-7B2 levels were observed in patients with chronic renal failure (175.1 +/- 35.9pmol/liter). Some of the pregnant patients in their third trimester also showed high plasma IR-7B2 levels. A small but significant rise in plasma IR-7B2 was observed after a glucose load in control subjects and diabetics. Intravenous LH-RH exerted a rise in plasma 7B2 concentrations though arginine and TRH showed no significant effect on plasma IR-7B2 concentrations. Compared with the plasma concentrations, ten to fifty-fold high levels of IR-7B2 were observed in cerebrospinal fluid (CSF) from patients with cerebrovascular accidents or multiple sclerosis. These results suggested that the kidney plays a major role in 7B2 degradation and that LH-RH simulates IR-7B2 release from the pituitary gland. Whether reduced clearance or increased production was responsible for the IR-7B2 elevation in subjects under 10 years or over 70 years requires investigation. Furthermore, high levels of IR-7B2 in CSF might indicate its specific role for the central nervous system.

Recurrent Anaphylaxis in Menstruating Women

Recurrent idiopathic anaphylaxis is an illness consisting of recurring anaphylactic or anaphylactoid attacks of unknown cause. A patient has been described whose attacks appeared to be associated with endogenous progesterone secretion and who was treated successfully with an analog of luteinizing hormone-releasing hormone (LHRH). This report summarizes the treatment of four additional women with recurrent anaphylaxis in a randomized, double-blind trial of an LHRH agonist and placebo. Two out of the four women experienced remission of their symptoms with the LHRH analog. The patients who responded to therapy had experienced systemic anaphylactoid reactions after provocation with an LHRH infusion and the intradermal injection of medroxyprogesterone; the nonresponders had no adverse reactions to either challenge. Ovarian suppression with LHRH agonist may benefit a subset of women with recurrent idiopathic anaphylaxis.

Episodic luteinizing-hormone release in the ovariectomized female guinea pig: rapid inhibition by estrogen.

Negative feedback of estrogen was investigated in ovariectomized female guinea pigs. Two weeks after ovariectomy, indwelling catheters were inserted into the jugular vein, and 3 days later, blood samples were taken every 10 min to determine the pattern of luteinizing hormone (LH) secretion. LH secretion in these guinea pigs was episodic, with a mean pulse period of 32 min. The mean pulse amplitude was 2.1 ng/ml, with mean plasma LH levels of 1.8 ng/ml. Twenty-five micrograms 17 beta-estradiol (E2), given i.v., caused a pronounced inhibition of pulsatile LH release. Twenty-five microliters of 100% ethanol (vehicle) had no effect on plasma LH values. In a second set of experiments, ovariectomized female guinea pigs were given two injections of luteinizing hormone-releasing hormone (LHRH) (1 microgram/kg BW, i.v.) separated by 30 min. Sharp rises in serum LH values were detected after each injection. A third injection of LHRH was administered after an injection of either 25 micrograms E2 or 25 microliters vehicle. In the presence of E2, the LH response was significantly (p less than 0.005) diminished, whereas the vehicle did not change the LH response to LHRH. These rapid effects of E2 on LH secretion and the pituitary responsiveness to LHRH infusion indicate that in the ovariectomized guinea pig E2 can directly block gonadotropin secretion. These findings are consistent with the hypothesis that negative feedback actions of E2 are directly on the membrane of the gonadotrope.

Effect of [ d-Trp 6]LHRH infusion on prolactin secretion by perifused rat pituitary cells

The effect of a superactive agonistic analog of luteinizing hormone-releasing hormone (LHRH), [ d-Trp 6]LHRH on prolactin (PRL) secretion by perifused rat pituitary cells was investigated. Constant infusion of [ d-Trp 6]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-Trp 6]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 μg of [ d-Trp 6]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-Trp 6]LHRH infusion period. On the other hand, thyrotropin-releasing hormone (TRH)-stimulated PRL secretion was slightly, but significantly impaired by [ d-Trp 6]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-Trp 6]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.

Suppression by LRH of the stimulatory effect of oestradiol on the secretion of LH by the rat pituitary gland.

Ovariectomized rats were infused with varying doses of luteinizing hormone-releasing-hormone (LRH). Some of the rats were also treated with oestradiol benzoate (EB). The effects of these pre-treatments on the in vitro release of luteinizing hormone (LH) were studied. The following parameters of in vitro LH release were measured: the autonomous secretion rate; the secretion rate following maximum stimulation with LRH, and the total quantity of LH released during the 6-hour experiment. The in vivo pre-treatments with LRH and EB dose-dependently decreased the pituitary LH content as well as all three of the above parameters of in vitro LH secretion. There was a linear relationship between the pituitary LH content and the three parameters of in vitro LH release. These parameters were therefore expressed as percentage of the pituitary LH content to give the relative LH secretion rates. The three parameters were thereby corrected for LRH/EB-induced changes in the pituitary LH content. In this way we obtained information on the effects of LRH and EB on the state of the LH release mechanisms of the gonadotropes. EB potentiated the LRH-induced depletion of the pituitary LH stores at all in vivo LRH infusion rates. The effect of EB on the quantity of LH released during perifusion in vitro, however, varied with the previous LRH infusion rates. After LRH infusion rates lower than about 120 ng/h (which establishes plasma concentrations of about 70 ng/l) EB enhanced the stimulated quantity of LH released. After higher rates of LRH infusion, EB lowered the amount of LH released.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Exposure to alcohol in utero alters the adult patterns of luteinizing hormone secretion in male and female rats

Luteinizing hormone (LH) secretory patterns were characterized in adult male and female rats exposed to ethanol during the last week of fetal life. Gonadectomized fetal alcohol exposed (FAE) males and females had significantly reduced plasma LH titers as compared to those of pair-fed (PF) controls. The phasic afternoon LH secretory response to estrogen and progesterone priming was also significantly reduced in FAE females. These differences do not appear to be a result of altered pituitary sensitivity to luteinizing hormone releasing hormone (LHRH), since the infusion of LHRH resulted in an equal response in PF and FAE females. Subsequent characterization of the episodic pattern of LH secretion in FAe males revealed significantly reduced mean LH level as well as a decreased pulse amplitude and frequency when compared to PF males. Taken together, these data indicate that some of the central mechanisms controlling pituitary LH secretion are altered by prenatal exposure to alcohol.

Pulsatile infusion of luteinizing hormone-releasing hormone: Effects on luteinizing hormone secretion and ovarian function in prepuberal gilts

Ten intact and hypophysial stalk-transected (HST), prepuberal Yorkshire gilts, 112–160 days old, were subjected to a pulsatile infusion regimen of luteinizing hormone-releasing hormone (LHRH) to investigate secretion profiles of luteinizing hormone (LH) and ovarian function. A catheter was implanted in a common carotid artery and connected to an infusion pump and recycling timer, whereas an indwelling external jugular catheter allowed collection of sequential blood samples for radioimmunoassay of LH and progesterone. In a dose response study, intracarotid injection of 5 μg LHRH induced peak LH release (5.9 ± 0.65 ng/ml; mean ± SE) within 20 min, which was greater ( P < 0.001) than during the preinjection period (0.7 ± 0.65 ng/ml). After HST, 5 μg LHRH elicited LH release in only one of three prepuberal gilts. Four intact animals were infused with 5 μg LHRH (in 0.1% gel phosphate buffer saline, PBS) in 0.5-ml pulses (0.1 ml/min) at 1.5-h intervals continuously during 12 days. Daily blood samples were obtained at 20-min intervals 1 h before and 5, 10, 20, 40, 60 and 80 min after one LHRH infusion. Plasma LH release occurred in response to pulsatile LHRH infusion during the 12-day period; circulating LH during 60 min before onset of LHRH infusion was 0.7 ± 0.16 ng/ml compared with 1.3 ± 0.16 ng/ml during 60 min after onset of infusion ( P < 0.001). Only one of four intact gilts ovulated, however, in response to LHRH infusion. This animal was 159 days old, and successive estrous cycles did not recur after LHRH infusion was discontinued. Puberal estrus occurred at 252 ± 7 days in these gilts and was confirmed by plasma progesterone levels. These results indicate that intracarotid infusion of 5 μg LHRH elicits LH release in the intact prepuberal gilt, but this dosage is insufficient to cause a consistent response after HST.

Effects of Intermittent Pulsatile Infusion of Luteinizing Hormonereleasing 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.

Effect of aromatase inhibition by Δ1-testolactone on basal and luteinizing hormone-releasing hormone-stimulated pituitary and gonadal hormonal function in oligospermic men

Aromatase inhibition by delta 1-testolactone (TL), 500 mg twice daily for 4 weeks, in nine patients with idiopathic oligospermia lowered circulating estradiol (E2) levels by about 30%, enhanced the secretion of follicle-stimulating hormone (+ 30%), 17-hydroxyprogesterone (17-OHP) (+ 40%), and testosterone (T) (+ 30%), but did not affect serum luteinizing hormone levels. Despite E2 lowering, there was an accumulation of 17-OHP over T, suggesting 17, 20-lyase inhibition. Unexpectedly, administration of TL almost completely deleted the T response to continuous luteinizing hormone-releasing hormone infusion present before TL therapy, despite similar gonadotropin release. Because the 17-OHP response to the luteinizing hormone-releasing hormone infusion was even higher during therapy, the 17,20-lyase lesion seemed aggravated despite substantial reduction of E2 levels. Although the present data suggest that estrogens play a less dominant role in the origin of the late steroidogenetic lesion than previously assumed, the suggestion also arises that TL per se, in addition to its antiestrogenic action, exerts an inhibiting effect on the 17,20-lyase locus, which may obscure the beneficial effect of reducing E2.

Effects of pulsatile infusion of luteinizing hormone-releasing hormone on luteinizing hormone secretion and ovarian function in hypophysial stalk-transected beef heifers.

Hypothalamic regulation of luteinizing hormone (LH) secretion and ovarian function were investigated in beef heifers by infusing LH-releasing hormone (LHRH) in a pulsatile manner (1 microgram/ml; 1 ml during 1 min every h) into the external jugular vein of 10 hypophysial stalk-transected (HST) animals. The heifers were HST approximately 30 mo earlier. All heifers had increased ovarian size during the LHRH infusion. The maximum ovarian size (16 +/- 2.7 cm3) was greater (P less than 0.01) than the initial ovarian size (8 +/- 1.4 cm3). Ovarian follicular growth occurred in 4 of 10 HST heifers in response to pulsatile LHRH infusion. In 2 heifers, an ovarian follicle developed to preovulatory size, but ovulation occurred in only 1 animal after the frequency of LHRH was increased (1 microgram every 20 min during 8 h). In blood samples obtained at 20-min intervals every 5th day, LH concentrations in peripheral serum remained consistently low (0.9 ng/ml) and nonepisodic in the 10 HST heifers during infusion of vehicle on the day before beginning LHRH. In 7 of 10 HST animals, episodic LH secretion occurred in response to pulsatile infusion of LHRH. In 3 of these long-term HST heifers, however, serum LH remained at basal levels and the isolated pituitary seemingly was unresponsive to pulsatile infusion of LHRH as indicated by sequential patterns of gonadotropin secretion obtained at 5-day intervals. These results indicate that pulsatile infusion of LHRH induces LH release in HST beef heifers.

Differential effect of luteinizing hormone-releasing hormone infusion on testicular steroids in normal men and patients with idiopathic oligospermia

Basal serum gonadotropin levels in 11 oligospermic men were significantly higher than in 9 euspermic control subjects, although most were still in the normal range. Basal serum testosterone (T), 17-hydroxyprogesterone (17-OHP), and estradiol levels and their ratios did not differ significantly. Continuous luteinizing hormone-releasing hormone (LH-RH) infusion (1 microgram/minute for 180 minutes) during integrated blood sampling evoked similar gonadotropin responses in both groups but had a differential effect on T: in the control subjects T increased (P less than 0.01) within 15 minutes to 1.5 times baseline, whereas in the oligospermic men T decreased (P less than 0.01). From 60 minutes on, however, T also significantly rose in the oligospermic men, but the maximum increment was about half lower (P less than 0.01) than in the euspermic men, despite virtually similar rises in 17-OHP. Only in the oligospermic men did the 17-OHP/T ratio increase (P less than 0.02) during LH-RH, which is compatible with the occurrence of a 17,20-lyase block. Serum estradiol did not increase in either group. In conclusion, continuous LH-RH infusion uncovers an intrinsic difference in acute Leydig cell stimulation between euspermic and oligospermic men.