LH Surge In Response Research Articles

The differential secretion of FSH and LH: regulation through genes, feedback and packaging

While the role of oestradiol and progesterone in the control of GnRH pulsatile secretion and generation of the preovulatory GnRH surge to induce release of the LH surge has been fully investigated, less attention has been given to changes in the pituitary gland that may sensitize gonadotrophs to switch from pulsatile release to surge release of LH, in particular. Furthermore, in the follicular phase while pulsatile secretion of LH is maximal, FSH secretion is reduced, yet both hormones are produced by the same gonadotrophs. The mechanisms whereby this differential release can occur are still unclear. The main regulator of FSH secretion is through the negative feedback effects of oestradiol and inhibin, which directly affect FSHbeta mRNA content and subsequent synthesis of FSH. FSH is then released predominantly via a constitutive pathway and the amount released is closely related to the rate of synthesis. In contrast, while basal LH secretion occurs via a constitutive pathway, the principal release of LH through pulsatile secretion is through the regulated pathway with GnRH stimulating the release of pre-synthesized LH contained in storage granules without significant changes in LHbeta mRNA. Secretogranin II (SgII) is associated with LH in these electron-dense storage granules and LH-SgII granules appear to be the principal form of granule released in response to GnRH through the regulated pathway. At the time of the preovulatory LH surge, granule movement to the gonadotrope cell membrane abutting a capillary, polarization, appears to play an important part in the priming mechanism for release of LH during the preovulatory LH surge in response to the GnRH surge. As there appears to be limited or no gonadotroph cell division in the adult pituitary gland, each gonadotroph passes through this synthesis and secretion pathway repeatedly through successive oestrous cycles. Packaging of LH and FSH into different secretory granules within the same cell is thus pivotal for the differential secretion of these gonadotrophins.

Loss of Fertility in the Absence of Progesterone Receptor Expression in Kisspeptin Neurons of Female Mice.

Ovarian steroids, estradiol and progesterone, play central roles in regulating female reproduction by acting as both positive and negative regulators of gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. Recent studies have identified kisspeptin neurons of the hypothalamus as the target of estrogenic regulation of GnRH secretion. In this study, we aimed to determine the significance of progesterone receptor (PGR) expression in the kisspeptin neurons. To this end, the Pgr gene was selectively ablated in mouse kisspeptin neurons and the reproductive consequence assessed. The hypothalamus of the Pgr deficient female mouse expressed kisspeptin, the pituitary released LH in response to GnRH stimulation, and the ovary ovulated when stimulated with gonadotropins. However, the mutant mouse gradually lost cyclicity, was unable to generate a LH surge in response to rising estradiol, and eventually became infertile. Taken together, these results indicate that the loss of PGR impairs kisspeptin secretory machinery and therefore that PGR plays a critical role in regulating kisspeptin secretion.

Estudio del eje hipotalamo-hipofisis-ovario, en la hemorragia uterina disfuncional

Se ha estudiado la interrelación de hipotálamo-hipófisis y ovario durante tres meses, en tres casos de mujeres jóvenes con hemorragia uterina disfuncional, mediante determinaciones radioinmunológicas seriados en plasma de FSH, LH, estradiol y progesterona. En 2 de las pacientes se observaron ciclos a novulatorios, incluso después de administrar citrato de clomifeno, presentándose falla al menos parcial, en la descarga de LH como respuesta a los marcados incrementos, aunque irregulares, del estradiol, procedente de secreción folicular adicional. En un caso se presentó probable ciclo ovulatorio espontáneo y después inducido por clomifeno. A su vez, las elevaciones plasmáticas de LH y FSH, encontradas durante el tratamiento con el clomifeno y subsiguiente desarrollo folicular, indicarían que se mantuvo indemne el mecanismo del feedback negativo entre el estrógeno y las gonadotrofinas. A juzgar por estos hallazgos, pareciera que hay cambios en la sensibilidad del hipotálamo, de ciclo a ciclo, en la hemorragia uterina disfuncional de la adolescencia.

Risk Factors for Failure to Respond to GnRH Agonist Trigger in Fresh In Vitro Fertilization Cycles

Gonadotropin-releasing hormone (GnRH) agonists are often used to trigger ovulation during IVF in order to decrease the risk of ovarian hyperstimulation syndrome in high responders. Administration of a GnRH agonist trigger in antagonist cycles causes an endogenous LH surge that promotes follicular maturation prior to oocyte retrieval. Rare instances of failure to mount an appropriate LH surge in response to an agonist trigger have been reported, an event associated with decreased oocyte maturity, low oocyte yield, and compromised cycle outcomes.

LH surge in response to the treatment with GnRH analog or estradiol in ovariectomized buffaloes with or without progesterone pre-exposition

The aim of the present study was to evaluate the LH surge after EB (estradiol benzoate) or GnRH administration with or without P4 (progesterone) pre-exposure in ovariectomized (OVX) buffalo cows. Females were randomly assigned to receive an intravaginal P4 device (D0–D9). They were then given EB 24h or GnRH 36h post-P4 device removal (factorial 2×2, n=6 per group). Blood collection for LH measurement began 36h after the P4 device removal and continued at 3h intervals. The area under the LH curve (AUC; 30.2ng2 and 13.41ng2; P=0.007) and the area of the LH peak (AP; 19.0ng2 and 8.9ng2; P=0.009) were greater for EB than GnRH. We did not observe an effect of P4 pre-exposure on the AUC and AP. Furthermore, there was no interaction between P4 pre-exposure and EB or GnRH treatment on the AUC and AP. However, there was an interaction (P<0.01) between P4 pre-exposure and the type of inducer (EB or GnRH) to release a preovulatory-like LH surge at the beginning (BP), final (FP) and time (TP) of the LH peak. The P4 pre-exposure anticipated the BP (2.5 and 7.4h), TP (6.0 and 12.0h) and FP (11.5 and 17.1h) when EB was used to induce a preovulatory-like LH surge (P<0.01). However, there was no effect of P4 pre-exposure on BP (0.4 and 0.4h), TP (3.0 and 3.0h) and FP (5.9 and 6.1h) with GnRH treatment. There was also no effect of the pre-exposure to P4, type of inducer or interaction on the amplitude of the LH peak. We concluded that EB therefore led to greater LH release than GnRH, and pre-exposure to P4 before EB administration anticipated the preovulatory-like LH surge in buffalo cows.

Reduced responsiveness of kisspeptin neurons to estrogenic positive feedback associated with age-related disappearance of LH surge in middle-age female rats

Age-related disappearance of the LH surge is one of major biomarkers of reproductive aging in female rats. Kisspeptin neurons in the hypothalamic anteroventral periventricular nucleus (AVPV) are proposed as the critical regulator of the preovulatory LH surge in response to estrogenic positive feedback. Here we investigated the possible involvement of the AVPV kisspeptin neurons in the disappearance of the LH surge in middle-age rats. Middle-age rats exhibiting persistent estrus (M-PE) did not show an LH surge although neither Kiss1 mRNA nor peptide in the AVPV was differentially expressed when compared to young rats exhibiting normal estrous cycles (YN). M-PE released LH in response to exogenous kisspeptin in a similar dose-dependent manner as YN, suggesting that their GnRH neurons still maintained responsiveness to kisspeptin. To investigate the estrogenic positive feedback effect on kisspeptin neurons in the AVPV, rats were ovariectomized and supplemented with estradiol (OVX+E2). We performed in situ hybridization and immunohistochemistry for Kiss1 mRNA and cFos, respectively, and found that M-PE exhibited a significantly lower percentage of Kiss1 mRNA positive neurons with cFos immunoreactivity, although the total number of kisspeptin neurons was not different from that in cyclic rats. Furthermore, OVX+E2 M-PE did not show the surge-like LH release under high estradiol administration while YN did. Thus our current study suggests that the reduced responsiveness of the AVPV kisspeptin neurons to estrogenic positive feedback presumably results in the decrease in kisspeptin secretion from neurons and eventually causes the age-related disappearance of the LH surge in middle age female rats.

Genetic study of multigenic factors related to strain difference of temporal pattern in mouse home-cage activity

Age-related disappearance of the LH surge is one of major biomarkers of reproductive aging in female rats. Kisspeptin neurons in the hypothalamic anteroventral periventricular nucleus (AVPV) are proposed as the critical regulator of the preovulatory LH surge in response to estrogenic positive feedback. Here we investigated the possible involvement of the AVPV kisspeptin neurons in the disappearance of the LH surge in middle-age rats. Middle-age rats exhibiting persistent estrus (M-PE) did not show an LH surge although neither Kiss1 mRNA nor peptide in the AVPV was differentially expressed when compared to young rats exhibiting normal estrous cycles (YN). M-PE released LH in response to exogenous kisspeptin in a similar dose-dependent manner as YN, suggesting that their GnRH neurons still maintained responsiveness to kisspeptin. To investigate the estrogenic positive feedback effect on kisspeptin neurons in the AVPV, rats were ovariectomized and supplemented with estradiol (OVX + E2). We performed in situ hybridization and immunohistochemistry for Kiss1 mRNA and cFos, respectively, and found that M-PE exhibited a significantly lower percentage of Kiss1 mRNA positive neurons with cFos immunoreactivity, although the total number of kisspeptin neurons was not different from that in cyclic rats. Furthermore, OVX + E2 M-PE did not show the surge-like LH release under high estradiol administration while YN did. Thus our current study suggests that the reduced responsiveness of the AVPV kisspeptin neurons to estrogenic positive feedback presumably results in the decrease in kisspeptin secretion from neurons and eventually causes the age-related disappearance of the LH surge in middle age female rats.

Bovine model of reproductive aging: Response to ovarian synchronization and superstimulation

The responsiveness of the hypothalamo-pituitary axis to steroid treatments for ovarian synchronization and the ovarian superstimulatory response to exogenous FSH was compared in 13–14 year old cows and their 1–4 year old young daughters. We tested the hypotheses that aging in cattle is associated with: (1) decreased follicular wave synchrony after estradiol and progesterone treatment; (2) delayed LH surge and ovulation in response to exogenous preovulatory estradiol treatment; (3) reduced superstimulatory response to exogenous FSH. Higher plasma FSH concentrations ( P < 0.01), and a tendency ( P = 0.07) for fewer 4–5 mm follicles at wave emergence were observed in old cows ( n = 10) than in young cows ( n = 9). The suppressive effect of estradiol/progesterone treatment on FSH was similar between old and young cows. Although the preovulatory LH surge in response to estradiol treatment was delayed in old than young cows ( P = 0.01), detected ovulation times were not different. No difference in ovarian superstimulatory response was detected between age groups, but old cows ( n = 8) tended ( P = 0.10) to have fewer large follicles (≥9 mm) 12 h after last FSH treatment than in young cows ( n = 7). We concluded that pituitary and ovarian responsiveness to estradiol/progesterone synchronization treatment was similar between old and young cows, but aging was associated with a delayed preovulatory LH surge subsequent to estradiol treatment. Old cows tended to have fewer large follicles after superstimulatory treatment than young cows.

Formation of Follicular Cysts in Cattle and Therapeutic Effects of Controlled Internal Drug Release

Follicular cysts in cattle result from excessive growth of the dominant follicle without ovulation and still constitute a major reproductive disorder in this species. One key hormonal characteristic of cows with follicular cysts is the lack of an LH surge, although they have increased plasma estradiol concentrations. Another is a relatively high level of pulsatile secretion of LH that promotes continued growth of the dominant follicle. These LH characteristics seem to result from a functional abnormality in the feedback regulation of LH secretion by estradiol. Treatment with controlled internal drug release devices that increase circulating progesterone levels is effective in resolving follicular cystic conditions by 1) lowering pulsatile LH secretion and 2) restoring the ability of the hypothalamo-pituitary axis to generate an LH surge in response to an increase in circulating estradiol.

Fos expression in luteinizing hormone-releasing hormone neurons of guinea pigs, with knife cuts separating the preoptic area and the hypothalamus, demonstrating luteinizing hormone surges.

LHRH neurons in guinea pigs, as in primates and other non-rodent species, are broadly distributed in the basal forebrain. In this study, knife cuts were made in the anterior hypothalamus, effectively separating more caudally positioned hypothalamic LHRH neurons from those in rostral preoptic areas. Guinea pigs with knife cuts displayed an LH surge in response to steroid administration. There was no significant difference in the number of LHRH neurons that expressed Fos in conjunction with an LH surge, although fewer total LHRH neurons were detected in the forebrain of knife-cut versus sham-cut animals. Knife-cut animals displayed a larger percentage of LHRH/Fos neurons in one region of the caudal hypothalamus than sham-cut animals. The area and perimeter of the LHRH reaction product within the cytoplasm of LHRH/Fos neurons were smaller than those of single-labeled LHRH neurons in sham-cut animals and in the caudal hypothalamus, but not the rostral preoptic area, of knife-cut animals. We conclude that caudal hypothalamic LHRH neurons separated from rostral preoptic regions are capable of sustaining an LH surge in guinea pigs. This finding is important, as LHRH neurons are present in the caudal hypothalamus, as well as in preoptic areas, of a large number of mammalian species, including humans.

Effet de la progestérone sur le taux d'ovulation et la durée du cycle ovarien induits par effet mâle chez la brebis Barbarine et la chèvre locale tunisienne

Two experiments were conducted on 30 Barbarine ewes (Exp 1) and 40 local Tunisian goats (Exp 2) in seasonal anoestrus (May). In both experiments, half of the females received 20 mg of progesterone intramuscularly just before male introduction (day 0). Blood samples were taken at 4 h intervals from the time of introduction of the ram, for the determination of the time of the preovulatory LH surge in response to the 'ram effect' (Exp 1) and once a day from days 1 to 8 to determine plasmatic progesterone concentrations (Exp 1, Exp 2). The ovulation rate was determined by coelioscopy at days 4 and 9, and oestrus behaviour was monitored twice daily in each experiment. In the ewe, progesterone delayed the time of the preovulatory LH surge (58.8 +/- 10.1 vs 20.5 +/- 10.7 h, P < 0.001), and suppressed hypofunctional corpora lutea (0/15 vs 7/14, P < 0.001). The induced ovulation rate was not significantly different between control and treated females (1.50 +/- 0.52 vs 1.26 +/- 0.46 respectively). Only 1 female in the control group and 2 in the treated group showed oestrus behaviour at the induced ovulation. Suppression of short cycles by progesterone treatment allowed synchronization of oestrus between days 17 and 20 compared to days 14 and 23 in the control group (P < 0.001). In the goat, all induced ovulations in the control group were followed by a short cycle. In the progesterone-treated group, 3 out of 20 goats developed abnormal induced corpora lutea (P < 0.001). First oestrus occurred between days 1 and 8 in control group and between days 2 and 3 in treated goats. Treatment with progesterone increased the percentage of females showing oestrus at induced ovulation (100 vs 35%, P < 0.001). The ovulation rate at first oestrus was increased in treated goats (1.85 vs 1.35, P < 0.001). In conclusion, 20 mg progesterone administered at day 0 is efficient at preventing the occurrence of short ovarian cycles. After ovulation induced by the male effect, the percentage of females in oestrus, and the induced ovulation rate are increased by progesterone treatment.

Opioids and suckling in relation to inhibition of oestradiol-induced LH secretion in postpartum ewes

The effects of time postpartum and suckling status on the oestradiol-induced LH surge in ewes and some of the possible mechanisms involved were investigated. Lambs were removed from nonsuckled ewes at parturition (day 0) and the ewes hand-milked 12 and 48 h later to prevent discomfort. Nonsuckled ewes on day 1, 7, 14 or 28, and suckled ewes on day 7 or 28 postpartum were injected i.m. with 50 micrograms oestradiol benzoate (hour 0). A further eight suckled ewes were given oestradiol on day 1 (as above), and four were also given naloxone (1 mg kg-1 h-1) from 10 until 14 h after administration of oestradiol benzoate. There was no LH surge in response to oestradiol on day 1. In nonsuckled ewes the onset of the LH surge was significantly (P < 0.05) delayed when oestradiol was administered on day 7 (17.4 +/- 1.5 h), compared with when it was injected on days 14 and 28 postpartum (14.4 +/- 1.7 and 14.0 +/- 1.4 h). The LH surge was also delayed (P < 0.05) when oestradiol was administered on day 7 (18.0 +/- 2.8 h) in suckled ewes. There was no difference in the duration or amplitude of the LH surge with time postpartum in nonsuckled ewes. Suckling significantly (P < 0.05) reduced the amplitude of the LH surge on both day 7 (21.0 +/- 2.4 versus 26.4 +/- 2.3 ng ml-1) and day 28 (23.6 +/- 3.2 versus 28.8 +/- 2.9 ng ml-1), but had no effect on the onset or duration of the surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between an increase in plasma cortisol during transport-induced stress and failure of oestradiol to induce a luteinising hormone surge in dairy cows

This study investigated whether the stress associated with a 30-minute journey in a truck could distort the oestradiol-induced surge of luteinising hormone (LH) in dairy cows. Altogether 20 journeys were monitored, 16 to 18 hours after intramuscular administration of 1 mg oestradiol benzoate (OE2). Plasma cortisol concentration was elevated (P less than 0.001) within 30 minutes of the start of each journey, even when the journey was repeated at about weekly intervals, indicating a lack of habituation. The LH surge in response to 11 OE2 treatments in nine non-cycling cows within 30 days after calving was either absent (one cow) or significantly delayed, of shorter duration or of lesser amplitude following transport, compared with untransported OE2-treated controls. However, in six cycling cows, 58 days or more after calving, transport affected the LH surge only once. Even in these cows, the LH surge did not start until the cortisol concentration returned to normal, which may suggest a transient postponement of the LH surge by transport. In conclusion, transport impaired the LH surge in early post partum cows with little or no effect after ovarian cyclicity was resumed. It is hypothesised that endocrine events leading to the onset of the LH surge are more vulnerable to stressors in early post partum cows and in the natural situation this might be responsible for the occurrence of anovulation and cystic ovarian disease.

Effects of naloxone on the oestradiol-induced LH surge and cortisol release in transported cows.

Four control cows released a normal LH surge in response to 1 mg oestradiol benzoate i.m. Compared to controls, 30 min transport of 5 cows 16-18 h after oestradiol significantly delayed the onset (P less than 0.05), suppressed the amplitude (P less than 0.01) and reduced the total LH release (P less than 0.001) in 4 cows and totally blocked the surge in the 5th cow. Just before the onset of transport, 5 cows were given 250 mg naloxone i.v. In 3 cows, the LH surge was delayed and reduced in amplitude and duration and was totally blocked in the other two, i.e. naloxone did not avert the detrimental effects of transport. Transport stimulated cortisol release in cows. Cows given naloxone + transport released significantly more (P less than 0.001) cortisol than did those subjected to transport alone. In conclusion, naloxone appeared to have further stimulated the hypothalamopituitary-adrenal axis of cows under stress.

Posterior hypothalamic lesions advance the time of the pubertal changes in luteinizing hormone release in ovariectomized female rhesus monkeys.

To examine further the relationship between developmental changes in LH release and the onset of puberty, effects of posterior hypothalamic lesions were tested in ovariectomized (OVX), sexually immature female monkeys. In OVX females (n = 3) with sham hypothalamic lesions basal LH levels were suppressed during the prepubertal period until 25 months of age, when LH levels started to increase. The increase in basal LH continued; a 100% elevation from prepubertal levels was attained at 26.0 +/- 0 months of age, and a 200% elevation was attained at 31.0 +/- 3.2 months of age. A consistent appearance of LH circadian fluctuation (nocturnal LH increase) with a large amplitude accompanied the initial LH increase. Lesions of the posterior hypothalamus (PH) in OVX animals (n = 6) at 17-18 months of age, which we previously reported to be effective in advancing the onset of puberty by several months in ovarian intact monkeys, resulted in an early 100% increase in basal LH levels and the circadian LH fluctuation (19.5 +/- 1.0 months of age). Basal LH levels in these animals further increased, reaching a 200% elevation of prelesion levels at 24.2 +/- 0.7 months of age. All of these LH changes with PH lesions occurred significantly (P less than 0.01) earlier than those in sham-lesioned animals. Lesion of the PH in OVX animals (n = 4) at 13-14 months of age resulted in an increase in LH and the circadian LH fluctuation within 1 month postoperatively. However, 100% and 200% LH elevations did not occur until 20.8 +/- 1.0 and 24.8 +/- 1.4 months of age, respectively. These ages were similar to those of animals receiving lesions at 17-18 months of age, but much younger than those of sham controls (P less than 0.01). PH lesions in animals at 13-14 months of age also advanced the time of the first positive feedback effects of estrogen. In animals (n = 4) with PH lesions, estradiol benzoate induced a first LH response at 21.5 +/- 1.6 months of age, when basal LH was 276 +/- 83% increased from prelesion levels. This age was significantly (P less than 0.05) younger than that (29.3 +/- 1.9 months; n = 6) of the first LH surge induced by estrogen in control animals when basal LH levels attained 248 +/- 18% of prepubertal levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of sex steroids on the positive estrogen feedback mechanism in intact women and castrate men.

We studied the effects of prolonged testosterone treatment on ovulatory function and positive estrogen feedback in women and of prolonged estrogen priming on gonadotropin feedback in castrate men. An estrogen provocation test was carried out in 4 groups of transsexual subjects: 12 female transsexuals in their early follicular phase (days 3-5; group 1A), 8 females who had been treated with Depo-testosterone (T) for 3-6 months (group 1B), 11 men who had been castrated 3 months previously (group 2A), and 4 male castrates treated with oral estrogen for 3 months starting 3 months after castration (group 2B). The estrogen provocation test consisted of 3 GnRH tests (100 micrograms) carried out immediately before (0 h) and 44 and 92 h after an im injection of estradiol valerate (10 mg). Responses to the estrogen provocation test in women with normal menstrual cycles (group 1A) were typically female. After initial suppression at 44 h, a LH surge (positive feedback) occurred at 92 h. Pituitary responsiveness, however, was amplified both at 44 and 92 h. Prolonged T priming of women in group 1B did not inhibit the estrogen-induced LH surge, nor was the amplitude of the surge blunted. Removal of androgens and other testicular factors (group 2A) did not result in the appearance of an estrogen-induced LH surge. On the other hand, prolonged estrogen priming in male castrates (group 2B) resulted in activation of the positive feedback mechanism; a LH surge in response to the estrogen provocation occurred. The results of the present study imply that 1) contrary to an earlier suggestion, testosterone does not block or blunt the LH surge, indicating that it is probably not responsible for suppressing the LH surge in normal men; 2) testosterone can cause ovulatory failure without suppressing the LH surge in women; and 3) prolonged estrogen priming may be involved in activation of the positive feedback mechanism in humans.

Luteinizing hormone release in the cat in response to coitus on consecutive days of estrus.

Domestic cats are known to release an ovulatory LH surge in response to coitus. In this study, we determined the LH release following coitus on consecutive days of estrus. Variable responses to 2 matings were obtained as to the day of the ovulatory LH release: 6/14 on Day 1 (the first day of estrus), 3/14 on Day 2, 4/14 on Day 3 and 1/14 on Day 4 of estrus. The average amount of LH released during the ovulatory surge was 298 ng/ml X h (area units). The ovulatory surge was the greatest surge during estrus in 10/14 observations; 4/14 had a greater LH surge the following day. The average amount of LH released on the day of the greatest surge was approximately 338 ng/ml X h with significantly less (P less than 0.05) LH released on subsequent days: 33, 14, 19, 7 and 14 ng/ml X h. This dramatic decrease in LH release indicates an apparent refractoriness of the hypothalamus/pituitary to coital stimulation following a major release of LH. Estradiol-17 beta concentrations were always greater on the day of the coitus-induced ovulatory LH surge (mean = 51 +/- 5 pg/ml) as compared to the previous day (mean = 34 +/- 4 pg/ml) when coitus did not result in a significant LH release. These data suggest that the ability to release LH in response to coitus is in part a function of the duration of exposure to estrogen by the hypothalamus and/or anterior pituitary.

POSITIVE FEEDBACK OF OESTROGEN ON LH SECRETION IN WOMEN ON NEUROLEPTIC DRUGS

The effect of a-adrenergic and dopaminergic blockade on the ability of pituitary-hypothalamic axis to produce an LH surge in response to oestrogen, was studied in eleven women treated with the neuroleptic agents haloperidol, fluphenazine or chlorpromazine. Seven women on no medication were controls. 6.6 mg of oestradiol benzoate (OB) was injected i.m. after control serum was obtained and daily serum samples were obtained for four additional days. Sera were assayed for total oestrogens, LH, FSH and prolactin. Six of seven women in the control group and eight of eleven women treated with neuroleptic agents had LH surges to OB challenge. The mean prolactin of the treated women was 33.1 +/- 3.6(SEM) ng/ml and the mean prolactin of the controls was 14.9 +/- 1.5(SEM) ng/ml, P less than 0.005). Elevated levels of circulating prolactin did not prevent an LH surge to OB challenge. These results indicate that even in subjects with catecholamine blockade, an LH surge can be induced. This contrasts to results obtained in rats and suggests that the control mechanism of LH surge production differs in rodents and humans.

EFFECT OF CHRONIC ADMINISTRATION OF GONADOTROPHIN RELEASING HORMONE AND THYROTROPHIN RELEASING HORMONE TO PUBERTAL BULLS ON PLASMA LUTEINIZING HORMONE, PROLACTIN AND TESTOSTERONE CONCENTRATIONS, THE NUMBER OF EPIDIDYMAL SPERM AND BODY WEIGHT

SUMMARY The experiment was designed to determine whether chronic administration of gonadotrophin releasing hormone (GnRH) plus thyrotrophin releasing hormone (TRH) to pubertal bulls would hasten sexual maturation. Nine bulls, three each at 4, 5 and 6 months of age were given i.m. injections of GnRH (0·4 μg/kg) plus TRH (2 μg/kg) three times daily (09.00, 16.00 and 23.00 h) for 30 days. Equivalent animals were given 0·9% saline vehicle as controls. At the outset of injections the 6-, 5- and 4-month-old bulls weighed 201, 157 and 169 kg respectively; equivalent weights at the final injection were 222, 186 and 198 kg. Plasma levels of LH, prolactin and testosterone were determined weekly around the injection given at 09.00 h. Twenty-four-hour plasma testosterone and LH profiles were obtained immediately after the last injection. The animals were unilaterally castrated at the end of this 24 h period and the second testis was removed 60 days later to assess testicular weights and epididymal sperm numbers. Surges of LH, testosterone and prolactin occurred throughout the experimental period in response to GnRH/TRH injection. The LH surge in response to the first injection was nearly fivefold larger than those measured at subsequent weekly intervals but prolactin and testosterone responses did not decline during the 28-day experimental period. Induced LH and prolactin peaks were larger than those occurring in the control bulls, but control animals produced an equivalent amount of testosterone. These bulls produced quasi-adult levels of testosterone even at 4 months of age. Chronic GnRH/TRH administration resulted in a depression of plasma testosterone, and a disruption of the normal episodic release pattern during the 24 h after the final treatment, but normal patterns returned within 60 days. Testicular weights and epididymal sperm numbers were not increased by chronic GnRH/TRH treatment.