Dose Of Luteinizing Hormone-releasing Hormone Research Articles

Short-term pituitary desensitization to luteinizing hormone-releasing hormone (LH-RH) after pulsatile LH-RH administration in women with amenorrhea of suprapituitary origin

The existence of a short-term pituitary desensitization in luteinizing hormone (LH) release to single doses of luteinizing hormone-releasing hormone (LH-RH) in the ovariectomized rat was recently disclosed. The purpose of the present study was to investigate whether this refractoriness is also present in humans. Blood from six women with amenorrhea of suprapituitary origin was sampled every 10 minutes for 300 minutes for determination of LH and follicle-stimulating hormone (FSH). A pulse of 20 micrograms LH-RH was given intravenously 90 and 210 minutes after the first blood sample, and 2 micrograms LH-RH was given 30, 150, 240, and 270 minutes after t0. The mean maximal increments of LH and FSH were compared. The LH response to a 2-micrograms LH-RH bolus given 30 (t240) or 60 (t150) minutes after a 20-micrograms LH-RH pulse was significantly decreased, compared with the initial response to this dose at t30. For both LH and FSH, the response to 2 micrograms LH-RH given 30 minutes after the 20-micrograms pulse (t240) was almost absent, compared with 60 (t150) minutes after the 20-micrograms dose. We conclude that a short-term pituitary refractoriness to LH-RH is present after administration of single pulses of LH-RH in women with amenorrhea of suprapituitary origin and pulses of LH-RH in the physiologic range (2 micrograms) given to these women do not always generate LH and FSH increments that are identifiable as significant hormone pulses.

Pharmacokinetics of intravenous luteinizing hormone-releasing hormone administration in men: effects of various dosages

Exogenous luteinizing hormone-releasing hormone (LH-RH) was intravenously administered as a single-bolus injection to 26 healthy normal men. LH-RH doses were selected at 1, 2.5, 5, and 20 micrograms for exploration of the optimum LH-RH dose to obtain adequate pituitary stimulation. Blood samples (for LH-RH and LH determinations) were collected at frequent intervals from 10 minutes before to 60 or 90 minutes after injection. LH-RH peak levels varied, in a dose-dependent way, between 119 +/- 16 and 517 +/- 70 ng/l. Peak values were all reached between 1 and 3 minutes after injection, and elimination occurred rapidly, with half-lives between 2.6 +/- 0.4 and 5.2 +/- 1.0 minutes. The area under the curves increased significantly (P less than 0.01) if the doses of LH-RH had been augmented from 1 to 20 micrograms. Maximum LH values were reached more rapidly in the low-dose (1 and 2.5 micrograms) experiments (between 13.5 and 16.3 minutes), with an obvious decline afterwards. The area under the LH curves increased (P less than 0.01) if the doses of LH-RH had been elevated from 1 to 2.5 micrograms, but no further increase of LH release occurred (P greater than or equal to 0.21) if LH-RH doses were further elevated from 2.5 to 20 micrograms. The current study demonstrates that a 2.5-micrograms intravenous LH-RH dose is best suited for an adequate pituitary stimulation in normal men.

Changes in Circulating Levels of Immunoreactive Follicle Stimulating Hormone, Luteinizing Hormone, and Testosterone During Sexual Development in the Rhesus Monkey, Macaca mulatta

Basal serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) and the responsiveness of these hormones to a challenge dose of luteinizing hormone releasing hormone (LHRH), were determined in juvenile, pubertal, and adult rhesus monkeys. The monkey gonadotrophins were analyzed using RIA reagents supplied by the World Health Organization (WHO) Special Programme of Human Reproduction. The FSH levels which were near the assay sensitivity in immature monkeys (2.4 +/- 0.8 ng/ml) showed a discernible increase in pubertal animals (6.4 +/- 1.8 ng/ml). Compared to other two age groups, the serum FSH concentration was markedly higher (16.1 +/- 1.8 ng/ml) in adults. Serum LH levels were below the detectable limits of the assay in juvenile monkeys but rose to 16.2 +/- 3.1 ng/ml in pubertal animals. When compared to pubertal animals, a two-fold increase in LH levels paralleled changes in serum LH during the three developmental stages. Response of serum gonadotrophins and T levels to a challenge dose of LHRH (2.5 micrograms; i.v.) was variable in the different age groups. The present data suggest: an asynchronous rise of FSH and LH during the pubertal period and a temporal correlation between the testicular size and FSH concentrations; the challenge dose of LHRH, which induces a significant rise in serum LH and T levels, fails to elicit an FSH response in all the three age groups; and the pubertal as compared to adult monkeys release significantly larger quantities of LH in response to exogenous LHRH.

Effect of estradiol on the pituitary response to intravenous stimulation with luteinizing hormone-releasing hormone in menopausal women

Five menopausal patients were submitted to stimulation with 100-micrograms doses of luteinizing hormone-releasing hormone (LH-RH) administered 120 minutes apart under three different types of conditions: (1) in a hypoestrogenic state (test 1); (2) in a hyperestrogenic state after acute intravenous bolus injection of 400 micrograms 17 beta-estradiol (E2) (test 2); (3) in a hyperestrogenic state after daily oral administration of 50 micrograms ethinyl E2 for 3 to 4 weeks (test 3). The results of the three tests showed that (1) the time needed to reach maximum LH values after LH-RH injection was longest in test 3; (2) the hormonal production rate (HPR) in test 1 was greatest after the first stimulus with LH-RH. In test 2, the two stimulations with LH-RH induced an equivalent HPR, whereas in test 3, the HPR was greatest after the second stimulation; (3) the correlation between basal LH values before LH-RH injection and the maximal values of the responses obtained after each injection changed throughout the experiment. In all three tests, the slope of the line (significant positive correlation) was always greater after the second stimulation. When the three tests were compared, the slope in test 3 was greater than in test 2, and the slope in test 2 greater than in test 1. These results clearly suggest the important role of estrogens in the regulation of LH release in women by acting not only at the hypothalamus but also at the pituitary level, and demonstrate a correlation between basal LH levels and the maximum response to LH-RH stimulation. This correlation is more marked during estrogen treatment and depends on the time of exposure to estrogen.

Gonadotropin and Testosterone Response in Prepubertal Boys with Hypospadias

Serum levels of luteinizing hormone and follicle-stimulating hormone before and after luteinizing hormone-releasing hormone stimulation, and levels of testosterone before and after 3 days of treatment with human chorionic gonadotropin were determined by radioimmunoassay in 98 boys with hypospadias (2 to 8 years old). The doses of luteinizing hormone-releasing hormone and human chorionic gonadotropin were calculated for body surface. The basal and peak levels of serum luteinizing hormone, follicle-stimulating hormone and testosterone in patients with hypospadias were compared with 9 endocrinologically normal boys of the same age without hypospadias. Luteinizing hormone response to luteinizing hormone-releasing hormone stimulation was significantly impaired in boys with hypospadias and also simple hypospadias (no associated anomaly). Basal levels of luteinizing hormone in boys with simple hypospadias and levels of follicle-stimulating hormone in patients with hypospadias were significantly low. The maximum testosterone response to human chorionic gonadotropin stimulation was significantly decreased in boys with severe hypospadias in direct proportion to the degree of hypospadias.

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.

Serum luteinizing hormone-releasing hormone (LH-RH) and gonadotropic hormones in men after a bolus dose of LH-RH: comparison of different doses and routes of administration

Serum levels of luteinizing hormone-releasing hormone (LH-RH), LH, and follicle-stimulating hormone (FSH) were measured for 60 minutes after 5- and 20-micrograms bolus doses of LH-RH given either intravenously or subcutaneously to 20 healthy men, for the study of LH-RH pharmacokinetics and the corresponding pituitary gonadotropin release. Intravenous (5- and 20-micrograms) LH-RH administration revealed much sharper LH-RH pulses, with significantly higher levels between 1 and 5 minutes (P less than 0.001) but lower levels between 30 and 60 minutes (P less than 0.05), compared with the subcutaneous route. No statistically significant differences were observed in the magnitude and time occurrence of maximum LH release or in the area under the LH response curves between intravenous and subcutaneous LH-RH administration, either in the 5-micrograms or in the 20-micrograms group. FSH responses were small and insignificant in all the performed tests. The intravenous route of administration seems preferential in therapeutic regimens that use pulsatile exogenous LH-RH, because the conditions of intermittent pituitary stimulation are more adequately fulfilled and the risk of dose accumulation is reduced. Furthermore, LH-RH doses of 5 micrograms are capable of producing adequate pituitary LH release, whereas increases in the pulse dose up to 20 micrograms seem to have no additional effects.

Possible negative ultra-short loop feedback of luteinizing hormone releasing hormone (LHRH) in the ovariectomized rat.

To determine if LHRH might act within the brain to modify its own release, repeated blood samples were removed from conscious ovariectomized rats and minute doses of LHRH were injected into the third ventricle (3V). The effect of these injections on plasma LH and FSH was measured by radioimmunoassay (RIA). The higher dose of intraventricular LHRH (10 ng in 2 microliter) induced an increase in plasma LH within 10 min after its injection. Plasma LH decreased for the next 60 min. This was followed by restoration of LH pulses characteristic of the ovariectomized rat. This dose of LHRH slightly elevated plasma FSH concentrations. In stark contrast, a 10 fold lower dose of 1 ng of LHRH injected into the ventricle resulted in a highly significant decrease of plasma LH at 10 min following injection, followed by return of LH pulsations. There was no effect on the pulsatile release of FSH. The results are interpreted to mean that at the higher dose, sufficient LHRH reached the site of origin of the hypophyseal portal vessels in the median eminence so that it diffused into portal vessels and was delivered to the gonadotrophs to induce LH release. In contrast, the lower dose provided sufficient hypothalamic concentrations of the peptide to suppress the discharge of the LHRH neurons, thereby leading to a decline in plasma LH, indicative of an ultrashort-loop negative feedback of LHRH to suppress its own release.

The effects of single-dose luteinizing hormone-releasing hormone on ovulatory menstrual function: support for a single luteinizing hormone- and follicle-stimulating hormone-releasing factor

Ten ovulatory women were followed with gonadotropin and steroid determinations through two cycles. They were given 500 micrograms of luteinizing hormone-releasing hormone (LH-RH) during the periovulatory period of the second cycle to determine whether ovulation could be facilitated without altering corpus luteum function. Successive cycles demonstrated concordance for patterns of gonadotropin and steroid secretion when studied as group means. Two control cycles and one treatment cycle were consistent with luteal phase defects. The use of a supramaximal dose of LH-RH in these women neither facilitated ovulation nor adversely affected luteal function. A significant linear correlation was noted between peak LH and follicle-stimulating hormone (FSH) values for the spontaneous surges. This same linear relationship was maintained for the LH and FSH responses to 500 micrograms LH-RH. The present data produce further evidence demonstrating that the secretion of LH and FSH appears to be modulated by gonadal steroids and under the permissive control of a single gonadotropin-releasing hormone.

Luteinizing hormone releasing hormone enhances proceptivity in a primate.

Luteinizing hormone releasing hormone (LHRH) administered to ovariectomized marmosets treated with a low dose of 17 beta-oestradiol significantly enhanced proceptivity within 2 h. Without oestradiol priming LHRH treatment did not produce this effect. The dose of LHRH given did not significantly alter plasma levels of cortisol or progesterone. The behavioural effect of this treatment is therefore likely to have been mediated via a direct central action rather than indirectly through stimulating adrenocortical steroid secretion. These results provide the first demonstration that LHRH can potentiate the proceptive behaviour of a female primate.

Interaction between the posterior pituitary and LHRH in the control of LH secretion

We have recently reported that the posterior lobe of the pituitary differentially inhibits the secretion of prolactin (PRL) and luteinizing hormone (LH), but not follicle stimulating hormone (FSH) throughout the estrous cycle. Removal of the posterior pituitary (posterior pituitary lobectomy) results in elevations of plasma LH on all days of the cycle except on diestrus-day-2. In the present study we examined: 1. whether the control of LH release involves an interaction between the posterior pituitary and hypothalamic luteinizing hormone-releasing hormone (LHRH), and 2. whether the elevation of LH seen following posterior lobectomy is due to the removal of a posterior pituitary substance(s) which alters anterior pituitary sensitivity to LHRH. In order to block the action of hypothalamic LHRH, a potent LHRH inhibitory analog (50 μg) was injected SC two hours prior to removal of the posterior pituitary in estrous rats. Administration of the inhibitory analog completely eliminated the elevation of plasma LH seen following posterior lobectomy, but did not alter the posterior lobectomy-induced rise of plasma PRL, or plasma FSH concentrations. In order to test whether anterior pituitary sensitivity to LHRH is altered by posterior lobectomy, a moderate dose of LHRH (15 ng) was administered to both posterior lobectomized and sham lobectomized estrous rats. The time-course and magnitude of the LH response to LHRH was similar in both groups. The results are consistent with the hypothesis that LH secretion is controlled by an interaction between hypothalamic LHRH and the posterior lobe of the pituitary, but this interaction does not appear to involve lobectomy-induced changes in anterior pituitary responsiveness to LHRH. It remains to be determined whether the posterior pituitary contains a substance(s) which is capable of altering hypothalamic release of LHRH.

The luteinizing hormone-releasing hormone (LHRH)-desensitized rat pituitary: luteinizing hormone responsiveness to LHRH in vitro.

Desensitization of the anterior pituitary has been observed after continuous infusion of LHRH or repetitive administration of LHRH at concentrations or frequencies exceeding physiological limits. We have studied the LH responsiveness of the LHRH-desensitized male rat anterior pituitary in a continuously perifused dispersed cell culture system. Infusion of 10 nM LHRH initially stimulated a 4- to 5-fold increase in LH secretion which became maximal at 6-9 min and which declined gradually to a preinfusion baseline over 6 h. Since the cells did not maintain peak levels of LH secretion in the presence of continuous exposure to LHRH, they were considered to be desensitized. These desensitized cells were studied to determine their LH responsiveness to LHRH. Cells desensitized by a 6-h LHRH infusion responded to four hourly LHRH boluses of 200 pm by releasing four statistically equal LH pulses. The response of desensitized cells to 200 pm LHRH was similar to that of 10 pm LHRH of nondesensitized cells. Furthermore, desensitized anterior pituitary cells responded to LHRH in a linear dose-dependent manner. The dose response of desensitized cells ranged from 75-500 pm, whereas for nondesensitized cells a dose response was observed from 1-75 pm. In addition, anterior pituitary cells desensitized with continuous LHRH infusion can respond to a second LHRH infusion of a greater concentration and become desensitized for a second time. These data suggest that the capacity of the pituitary gland to store and secrete LH while desensitized is similar to that of the nondesensitized anterior pituitary. The major difference between cells desensitized with LHRH and nondesensitized cells is that desensitized cells require a larger dose of LHRH to elicit a given LH response.

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.

Variations in the number of pituitary LHRH receptors correlated with altered responsiveness to LHRH

Isolated pituitary cells from metestrous, ovariectomized (OVX), and ovariectomized-estradiol treated (OVX-EB) rats were employed to study the gonadotropin response to luteinizing hormone-releasing hormone (LHRH) challenge and to quantitate LHRH receptors, using a labeled LHRH analog. Ovariectomy (3–4 weeks post castration) resulted in a reduction of LHRH receptor concentration from 34.4 ± 2.1 in metestrous females to 14.3 ± 0.9 fmoles/10 6 cells. Concomitantly, the luteinizing hormone (LH) response to a near-maximal dose of LHRH (5 ng/ml) decreased from a 3-fold stimulation in intact females to 1.13-fold stimulation in cells from OVX rats. Replacement therapy with EB (50 ug/rat for 2 days) to OVX rats restored LH response and LHRH binding sites (a 2.5-fold stimulation in LH secretion and 32.0 ± 2.1 fmoles/10 6 cells, respectively). The LH response to LHRH stimulation was not altered after one day of EB treatment although the number of LHRH binding sites was increased. The changes in the number of LHRH binding sites were not accompanied by any alterations in the affinity of the LHRH analog ( K d ≊ 0.5 × 10 −9 M ). It is concluded that variations in LHRH receptor number reflect the degree of pituitary sensitivity to LHRH and it may suggest that LHRH and estradiol modulation of gonadotropin release is mediated by these receptors.

A study of the first eight hours in the stabilization of plasma testosterone concentration in the hemicastrated rat.

Plasma levels of testosterone fell within 4 h after hemicastration in the mature male rat, and recovered within 8 h, without a compensatory rise in plasma LH from 5 to 480 min after surgery. Pulsatile release of LH was not observed in any group, suggesting the possibility that its alteration was not stimulating the single testis. Luteinizing hormone releasing hormone (LH-RH) stimulated plasma LH concentration equally in both control and hemicastrated rats, rising more sharply only in sham-hemicastrated rats treated with a low dose of LH-RH. Plasma LH rose significantly at the same time (6h after surgery) in both castrated (in one step) and hemicastrated rats which were castrated (in two steps). Bilateral denervation of the testis did not affect the response of plasma testosterone after hemicastration. There was a remarkably similar response in both plasma LH and testosterone levels to handling, blood collection, anaesthesia, sham-surgery and hemicastration separately or in combination. It was concluded that the response of testosterone to hemicastration was neither related to early changes in plasma LH levels nor to alterations in the hypothalamo-hypophysial axis.

Role of adrenal in control of gonadotropin secretion in the immature male rat.

A study was made of adrenal control of gonadotropin secretion during the prepubertal period. Male rats were adrenalectomized (ADX) or sham operated on day 26. The sensitivity of the hypothalamus/pituitary to the negative feedback effects of testosterone (T) was examined by simultaneously castrating the animals and implanting various size Silastic capsules filled with crystalline T. These animals were decapitated on day 30. Another group of immature rats was examined to determine pituitary sensitivity to luteinizing hormone releasing hormone (LHRH). These rats were ADX on day 26 and injected intravenously with various doses of LHRH on day 30. ADX did not alter the negative feedback of T on luteinizing hormone (LH) secretion or the ability of the pituitary to release LH in response to LHRH. ADX appeared to lower the set point for follicle stimulating hormone (FSH) secretion but not the ability of T to reduce FSH. Pituitaries of ADX rats released less FSH in response to LHRH than did controls. These results show the role of the adrenal in the control of FSH secretion in the prepubertal male rat.

Perifused pituitary cultures: a model for LHRH regulation of LH secretion.

In this paper, a dispersed anterior pituitary cell system that is continuously perifused and suitable for the study of luteinizing hormone-releasing hormone (LHRH)-anterior pituitary physiology is described. Adult male Sprague-Dawley rats were decapitated and the anterior pituitaries removed, dispersed using collagenase, mixed with Biogel P2, and packed into 0.9-cm columns using sterile technique. All experiments were conducted using Krebs-Ringer-bicarbonate-glucose buffer, and a stable base line was achieved. A constant dose of LHRH (50 ng) administered several times at 1-h intervals stimulated the same quantal release of LH. LH secretion is linear in response to LHRH over the range of 1-50 nM and to rat hypothalamic extracts over a range of 1/32 to 1/2 hypothalamic equivalents, regardless of whether the extracts are administered in ascending or descending order. These results indicate that perifusion of dispersed pituitary cells provides a useful model for the study of LHRH physiology, combining the advantages of the long-term viability of pituitary cells in culture with the dynamic nature afforded by perifusion.

Evaluation of pituitary responsiveness to LHRH as a pregnancy test in ewes

Pregnant and nonpregnant ewes were injected with luteinizing hormone-releasing hormone (LHRH). Pituitary responsiveness, based on serum luteinizing hormone (LH), and follicle stimulating hormone (FSH) concentration, 2 hr after injection was then determined for each ewe, by radioimmunoassay (RIA) and correlated with the physiological reproductive state of each ewe. The serum LH release in pregnant ewes was significantly lower than that in nonpregnant ewes. Serum LH concentrations of pregnant ewes were further categorized according to whether the ewes were multiple (ML) or single lambing (SL). The responses by ML ewes were lower for LH than the SL responses. Follicle stimulating hormone responses were not different between pregnant or nonpregnant groups. Luteinizing hormone responses between pregnant ewes which were grouped according to 3 stages of pregnancy (1 to 5, 5 to 10 and 10 to 15 weeks pregnant) were not different from each other. Pregnancy diagnoses were made based on a fixed cut-off value, to which the LH response of each ewe to 5 μg LHRH was compared. Ewes whose response fell below this cut-off were diagnosed as pregnant. Accuracy of the diagnoses were determined by known lambing data. Diagnostic accuracy ranged from a low of 60% for nonpregnant, to a high of 95% for ML ewes. Accuracy for SL ewes (64%) was lower than for the overall pregnant group (79%), as well as that for ML ewes. Doses of LHRH, higher than 5 μg per ewe, generally produced LH release in pregnant ewes which was not significantly suppressed relative to responses of nonpregnant ewes. These results lead to the conclusion that gonadotropin response to exogenous LHRH injection is not an effective tool for pregnancy diagnosis.

Increased LH secretory response to LHRH after hypophyseal stalk-transection of monkeys.

Luteinizing hormone-releasing hormone (LHRH) will evoke large increases of circulating LH in all species tested except for the rhesus monkey. Indeed, in the present study we found that an intravenous injection of a relatively large dose of LHRH (20 micrograms) evoked only a small (2.2-fold) increase in plasma LH levels, as measured by the dispersed interstitial cell bioassay in 4 intact follicular phase monkeys. In contrast, 4 stalk-transected animals exhibited a significantly greater (19.9-fold) increase in plasma LH levels when treated with 20 micrograms of LHRH within 1 week after surgery. Qualitatively similar differences in responsiveness also existed between the two treatment groups with respect to FSH secretion. 2 stalk-transected monkeys treated with LHRH at weekly intervals for the first 4 weeks after surgery showed progressive declines in the LH secretory response approaching, eventually, that observed in intact animals. In 3 additional monkeys, initiation of estrogen maintenance therapy within 3 h of stalk transection, to achieve mid-follicular phase plasma levels of estradiol, totally abolished hyperresponsiveness to LHRH. Thus, the results of this study demonstrate that a transient increase in pituitary responsiveness to LHRH occurs after hypophyseal stalk transection in rhesus monkeys. Although the results indicate that this phenomenon can be accounted for, in large part, by the absence of estrogen feedback, they do not preclude the possibility that factors other than LHRH and gonadal steroids regulate gonadotropin secretion in monkeys.

Pituitary refractoriness to luteinizing hormone releasing hormone: its importance in ending the luteinizing hormone surge in the cyclic rat.

AbstractA study was conducted to assess the importance of pituitary refractoriness to luteinizing hormone releasing hormone (LHRH) in ending the preovulatory surge of luteinizing hormone (LH) and in modulating the associated surge of follicle-stimulating hormone (FSH) in rat plasma. Phenobarbital-blocked proestrous rats were infused iv with LHRH at a constant rate of 50 ng/hr to restore the rising and plateau phases of the spontaneous surges of LH and FSH in plasma. Refractoriness to LHRH was demonstrated for LH but not FSH release when LHRH was infused beyond 2 hr. The plasma LH declined from high levels from 2 to 4.5 hr of infusion while the plasma FSH remained at an elevated plateau. The decline in plasma LH was not as rapid as that observed when the infusion was ended. Injection of a large dose (1 μg) of LHRH at 2 or 3.5 hr after the start of infusion caused substantial increases in plasma LH and FSH but only the LH response after the later injection was less than that observed in other rats given the...