Influence of the degree of stimulation of the pituitary by gonadotropin-releasing hormone on the action of inhibin and testosterone to suppress the secretion of the gonadotropins in rams

This experiment determined if the degree of stimulation of the pituitary gland by GnRH affects the suppressive actions of inhibin and testosterone on gonadotropin secretion in rams. Two groups (n = 5) of castrated adult rams underwent hypothalamopituitary disconnection and were given two i.v. injections of vehicle or 0.64 microg/kg of recombinant human inhibin A (rh-inhibin) 6 h apart when treated with i.m. injections of oil and testosterone propionate every 12 h for at least 7 days. Each treatment was administered when the rams were infused i.v. with 125 ng of GnRH every 4 h (i.e., slow-pulse frequency) and 125 ng of GnRH every hour (i.e., fast-pulse frequency). The FSH concentrations and LH pulse amplitude were lower and the LH concentrations higher during the fast GnRH pulse frequency. The GnRH pulse frequency did not influence the ability of rh-inhibin and testosterone to suppress FSH secretion. Testosterone did not affect LH secretion. Following rh-inhibin treatment, LH pulse amplitude decreased at the slow, but not at the fast, GnRH pulse frequency, and LH concentrations decreased at both GnRH pulse frequencies. We conclude that the degree of stimulation of the pituitary by GnRH does not influence the ability of inhibin or testosterone to suppress FSH secretion in rams. Inhibin may be capable of suppressing LH secretion under conditions of low GnRH.     

Plasma LH, FSH and testosterone concentrations in adult rams which were homozygous carriers or non-carriers of the Booroola fecundity gene

No gene-specific differences were found with respect to LH or testosterone pulsatile secretion (over 12 h), or in 12 hourly mean FSH concentrations in adult Booroola FF and ++ rams. Also, no differences between genotypes in the LH response to an injection of testosterone propionate, the FSH response to an infusion of bovine follicular fluid, or the testosterone response to injections of PMSG were noted. However, during the phase of seasonal testicular development, mean testosterone pulse amplitude (over 12 h) and the FSH response to 25 micrograms GnRH were higher in FF than in ++ rams (P less than 0.05); there were also significant effects of sire (P less than 0.05 in FF genotype only) and litter size (P less than 0.05) on testosterone pulse amplitude and GnRH-stimulated FSH release, respectively. During the breeding season, mean LH, but not FSH, concentrations were higher in FF than in ++ rams, after an injection of 0.5 micrograms GnRH; LH release was not affected by sire or litter size (P greater than 0.05). Long-term studies revealed that the FF rams were born in significantly larger litters, they weighed significantly less than ++ rams (P less than 0.05), and that bodyweight was significantly correlated (P less than 0.05) with litter size. There were no differences in testis size, and testis size was not significantly correlated with bodyweight. There was a strong tendency (P = 0.056) for overall mean FSH concentrations, measured weekly for 9 months, to be highest more often in FF than in ++ rams.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of gonadotropin-releasing hormone pulse-frequency modulation on luteinizing hormone, follicle-stimulating hormone and testosterone secretion in hypothalamo/pituitary-disconnected rams

The effects of changes in pulse frequency of exogenously infused gonadotropin-releasing hormone (GnRH) were investigated in 6 adult surgically hypothalamo/pituitary-disconnected (HPD) gonadal-intact rams. Ten-minute sampling in 16 normal animals prior to HPD showed endogenous luteinizing hormone (LH) pulses occurring every 2.3 h with a mean pulse amplitude of 1.11 +/- 0.06 (SEM) ng/ml. Mean testosterone and follicle-stimulating hormone (FSH) concentrations were 3.0 +/- 0.14 ng/ml and 0.85 +/- 0.10 ng/ml, respectively. Before HPD, increasing single doses of GnRH (50-500 ng) elicited a dose-dependent rise of LH, 50 ng producing a response of similar amplitude to those of spontaneous LH pulses. The effects of varying the pulse frequency of a 100-ng GnRH dose weekly was investigated in 6 HPD animals; the pulse intervals explored were those at 1, 2, and 4 h. The pulsatile GnRH treatment was commenced 2-6 days after HPD when plasma testosterone concentrations were in the castrate range (less than 0.5 ng/ml) in all animals. Pulsatile LH and testosterone secretion was reestablished in all animals in the first 7 days by 2-h GnRH pulses, but the maximal pulse amplitudes of both hormones were only 50 and 62%, respectively, of endogenous pulses in the pre-HPD state. The plasma FSH pattern was nonpulsatile and FSH concentrations gradually increased in the first 7 days, although not to the pre-HPD range. Increasing GnRH pulse frequency from 2- to 1-hour immediately increased the LH baseline and pulse amplitude. As testosterone concentrations increased, the LH responses declined in a reciprocal fashion between Days 2 and 7. FSH concentration decreased gradually over the 7 days at the 1-h pulse frequency. Slowing the GnRH pulse to a 4-h frequency produced a progressive fall in testosterone concentrations, even though LH baselines were unchanged and LH pulse amplitudes increased transiently. FSH concentrations were unaltered during the 4-h regime. These results show that 1) the pulsatile pattern of LH and testosterone secretion in HPD rams can be reestablished by exogenous GnRH, 2) the magnitude of LH, FSH, and testosterone secretion were not fully restored to pre-HPD levels by the GnRH dose of 100 ng per pulse, and 3) changes in GnRH pulse frequency alone can influence both gonadotropin and testosterone secretion in the HPD model.     

Effects of season and testosterone treatment on gonadotrophin secretion and pituitary responsiveness to gonadotrophin-releasing hormone in castrated Romney and Poll Dorset rams.

In castrated rams (Romney and Poll Dorset, n = 8 for each breed), inhibition by testosterone treatment (administered via Silastic capsules) of luteinizing hormone (LH) pulse frequency, basal and mean LH concentrations, mean follicle-stimulating hormone (FSH) concentration, and the peak and total LH responses to exogenous gonadotrophin-releasing hormone (GnRH) were significantly (P less than 0.01) greater during the nonbreeding than during the breeding season. Poll Dorset rams were less sensitive to testosterone treatment than Romney rams. In rams not receiving testosterone treatment, LH pulse frequency was significantly (P less than 0.05) lower during the nonbreeding season than during the breeding season in the Romneys (15.8 +/- 0.9 versus 12.0 +/- 0.4 pulses in 8 h), but not in the Poll Dorsets (13.6 +/- 1.2 versus 12.8 +/- 0.8 pulses in 8 h). It is concluded that, in rams, season influences gonadotrophin secretion through a steroid-independent effect (directly on hypothalamic GnRH secretion) and a steroid-dependent effect (indirectly on the sensitivity of the hypothalamo-pituitary axis to the negative feedback of testosterone). The magnitude of these effects appears to be related to the seasonality of the breed.     

Impact of season on seminal characteristics and endocrine status of adult free-ranging African buffalo (Syncerus caffer)

Pituitary, gonadal and adrenal activity were compared in free-living, adult African buffalo bulls during the breeding and nonbreeding seasons. Frequent blood samples were collected for 2 h from anaesthetized bulls treated intravenously with saline, gonadotrophin-releasing hormone (GnRH, 200 micrograms), human chorionic gonadotrophin (hCG, 10,000 i.u.) or adrenocorticotrophic hormone (ACTH, 1.5 mg). Electroejaculates also were collected from anaesthetized bulls during the breeding and nonbreeding seasons. Pretreatment testosterone concentrations among bulls varied more during the breeding (0.17-23.0 ng/ml) than the nonbreeding (0.15-2.21 ng/ml) season. The variation within the breeding season was attributed to 8 of 25 bulls producing higher (P less than 0.05) serum testosterone (High-T; 16.28 +/- 2.03 ng/ml) and testicular LH receptor (1.53 +/- 0.22 fmol/mg testis) concentrations compared with their seasonal counterparts (Low-T; 0.95 +/- 0.26 ng/ml; 0.38 +/- 0.04 fmol/mg) or with all bulls during the nonbreeding season (0.90 +/- 0.27 ng/ml; 0.31 +/- 0.04 fmol/mg). The magnitude of GnRH- and hCG-induced increases in serum testosterone was similar (P greater than 0.05) between Low-T bulls and bulls during the nonbreeding season. In the High-T animals treated with GnRH or hCG, serum testosterone did not increase, suggesting that secretion was already maximal. Peak serum LH concentrations after GnRH were greater (P less than 0.05) in bulls during the nonbreeding than the breeding season; FSH responses were similar (P greater than 0.05). ACTH treatment did not increase serum cortisol concentrations above the 2-fold increase measured in bulls treated with saline, hCG and GnRH (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of pituitary-adrenal-testis interaction in sheep. II. The effects of repeated injections of adrenocorticotrophic hormone outside the breeding season

The administration of 0.5 mg of long-acting adrenocorticotrophic hormone (ACTH, Synacthen-Depot) twice daily for 5.5 d to four rams outside the breeding season caused marked rises in plasma cortisol without any evidence of adrenal depletion. This treatment also caused marked rises in basal plasma follicle stimulating hormone (FSH) concentrations which remained high even after cessation of treatment. Plasma FSH responses to 5 ug of gonadotrophin releasing hormone (GnRH) were consistently observed and ACTH treatment increased the FSH response to GnRH. In contrast, spontaneous fluctuations in the plasma luteinizing hormone (LH) and testosterone concentrations were abolished by ACTH treatment. The quantity of testosterone released after GnRH (estimated by the maximum values reached and by the area under the response curve) was also suppressed while that of LH was only slightly lower. A comparison of the results of this experiment with those obtained in rams during the breeding season showed that the effects of ACTH on LH and testosterone were more marked during the breeding season. In contrast, the effect of ACTH on FSH is to increase the latter during the nonbreeding season, whereas no effect was observed during the breeding season.     

Effect of mouse epidermal growth factor on plasma concentrations of LH, FSH and testosterone in rams

Two experiments were conducted to examine the effects of mouse epidermal growth factor (EGF) on the concentrations of testosterone, LH and FSH in jugular blood plasma and on the pituitary responsiveness to LHRH. In 20 rams treated with subcutaneous doses of EGF at rates of 85, 98 or 113 micrograms/kg fleece-free body weight, mean plasma LH and testosterone concentrations were significantly reduced (P less than 0.05) at 6 h after treatment but not at 24 h. EGF treatment at 130 micrograms/kg fleece-free body weight suppressed the plasma content of these hormones for up to 48 h. Mean plasma FSH concentrations decreased significantly (P less than 0.05) for up to 48 h after EGF treatment, the effect being most pronounced in rams with mean pretreatment FSH values greater than or equal to 0.5 ng/ml. Intravenous injections of 1.0 micrograms LHRH given to each of 5 rams before and at 6 h, 24 h and 72 h after EGF treatment produced LH and testosterone release patterns which paralleled those obtained in 5 control rams similarly treated with LHRH. These results suggest that, in rams, depilatory doses of mouse EGF temporarily impair gonadotrophin and androgen secretion by inhibiting LHRH release from the hypothalamus. Such treatment appears to have no effect on the responsiveness of the pituitary to LHRH.     

Testosterone, luteinizing hormone, follicle stimulating hormone, and prolactin response to unilateral castration in prepubertal Holstein bulls

Hemicastration of Holstein bulls at 3 months of age resulted in increased (P<0.005) testicular weitht and testis sperm cell content at 330 days after treatment, but did not alter sperm cell concentration in the remaining hypertrophied testis. Radioimmuroassay of blood hormones at 1, 6, 12, and 24 weeks after treatment revealed that unilateral castration did not alter (P>0.1) basal levels or GnRH response profiles of either LH or testosterone compared to intact bulls. Hemicastration caused FSH to be elevated (P<0.01) compared to intact bulls at all sampling periods in both unstimulated and GnRH stimulated bulls. Prolactin varied with season and was greater (P<0.001) in hemicastrated bulls than in intact bulls at 1 and 6 weeks after treatment. Results indicate that unilateral castration at 3 months of age caused testicular hypertrophy of both steroidogenic and gametogenic function and this phenomena may be triggered by increased FSH or prolactin secretion, or both. Further, results indicate different testicular regulation mechanisms exist for pituitary LH and FSH release in bulls.     

Androgen and progesterone effects on follicle-stimulating hormone and luteinizing hormone secretion in anestrous mares

Anestrous lighthorse mares were treated in December with dihydrotestosterone (DHT; 150 micrograms/kg of body weight), progesterone (P; 164 micrograms/kg), both DHT and P (DHT+P), testosterone (T; 150 micrograms/kg), or vehicle (n = 4/group). Daily blood sampling was started on Day 1, and on Day 4 all mares were administered a pretreatment injection of gonadotropin-releasing hormone (GnRH) and were bled frequently to characterize the responses of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations. Treatment injections were given on Day 4 and then daily through Day 17. On Day 18, all mares were again administered GnRH and were bled frequently. Treatment of mares with DHT, P, or T increased (p less than 0.01) plasma concentrations of these steroids to approximately 1.5 ng/ml during the last 10 days of treatment. There was no effect (p greater than 0.10) of treatment on LH or FSH concentrations in daily blood samples. Relative to the pretreatment GnRH injection, mares treated with T or DHT+P secreted approximately 65% more (p less than 0.01) FSH in response to the post-treatment GnRH injection; FSH response to the second GnRH injection was not altered (p greater than 0.10) in control mares or in DHT- or P-treated mares. There was no effect of any steroid treatment on LH secretion after administration of GnRH (p greater than 0.10). Averaged over all mares, approximately 94 times more FSH than LH was secreted in response to injection of GnRH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of implanting bull calves with testosterone propionate, dihydrotestosterone propionate or oestradiol-17 beta prepubertally on the pituitary-testicular axis and on postpubertal social and sexual behaviour.

Twelve non-implanted crossbred bull calves served as controls and 30 crossbred bull calves (10/treatment) were implanted for 82 days, beginning at 34 days of age, to determine the influence of testosterone propionate (TP), dihydrotestosterone propionate (DHTP) and oestradiol-17 beta (E2) on prepubertal and pubertal pituitary-testicular function and on postpubertal social and sexual behaviour. Compared with control bulls, concentrations of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin concentrations were suppressed (P less than 0.01) in all implanted bulls. Testosterone (T) concentration increased (P less than 0.001) in TP-implanted, but decreased (P less than 0.01) in DHTP and E2 bulls during the implant period. LH response to gonadotrophin-releasing hormone (GnRH) challenge during the implant period (2.5 months of age) was less (P less than 0.01) in TP, E2 and DHTP bulls than in controls. A small but significant T response to GnRH occurred in control bulls at 2.5 months of age. LH and T responses to GnRH challenge at 7 months of age (100 days after implant removal) was similar (P greater than 0.20) in control and implanted bulls. Steroid implants administered prepubertally had no effect (P greater than 0.10) on postpubertal social and sexual behaviours, including number of flehmen responses, abortive mounts, services and competitive order score. Body weight did not differ (P greater than 0.10) between treatment groups, but testis size was reduced (P less than 0.01) during the implant period and up to 10 months of age in treated bulls compared with controls. Testes remained smaller in E2-treated bulls up to the end of the study (23 months of age), but daily sperm production and epididymal weight did not differ (P greater than 0.10) between treatment groups at slaughter. Control bulls reached puberty earlier (P less than 0.01; 270 +/- 11 days of age) than did TP (302 +/- 11 days), DHTP (309 +/- 11 days) or E2 (327 +/- 11 days) bulls. Although puberty was delayed in all implant groups, there was no difference in scrotal circumference at puberty (average 28.4 +/- 0.4 cm) between treatment groups. Our findings indicate that TP, DHTP and E2 implants administered prepubertally result in acute suppression of serum LH, FSH and inhibin during the implant period and in post-implant suppression of testis size and delayed puberty in bulls. The lack of treatment effect on behaviour suggests that steroidal programming of sexual behaviour occurs before 1 month of age in bulls.     

Short-term pituitary-testicular responses of prepubertal ram lambs to hemicastration

To examine the short-term effects of hemicastration on pituitary-gonadal responses, 12 ram lambs were anesthetized and hemicastrated at 4 mo of age and killed (n = 4) at 2 (HC2), 7 (HC7), or 14 (HC14) days following surgery. Four intact (INT) rams were killed 14 days following anesthesia. Testis and pituitary weights were similar between HC and INT rams. Serum follicle-stimulating hormone (FSH) in HC rams increased within 6 h, peaked at 12 h, and remained elevated above INT levels throughout the study. Overall mean serum testosterone levels in HC rams were lower than in INT rams for the first 48 h, but were similar by 3 days post-surgery. Pulsatile luteinizing hormone (LH) and testosterone secretion was suppressed for the first 9.5 h following anesthesia and/or surgery in both HC and INT animals. A single LH pulse and succeeding testosterone pulse occurred in 10/12 HC and 4/4 INT rams between 10 and 14 h post-surgery, both of which were lower in amplitude in HC than INT animals. However, on Day 7, pulsatile secretory patterns of LH and testosterone were similar, suggesting compensatory androgen secretion had occurred in HC rams. Pituitary LH content was unaffected by hemicastration. In contrast, pituitary FSH content was greater in HC7 and HC14 compared to HC2 and INT animals. Pituitary gonadotropin hormone-releasing hormone (GnRH) receptor concentrations were similar in INT, HC7, and HC14 rams, but were slightly reduced in HC2 rams. Neither testicular LH nor FSH receptor concentrations were altered by hemicastration at any time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the possible direct effects of gonadotrophin-releasing hormone analogues on the monkey (Macaca mulatta) testis

In Exp. 1, the effect of treatment with a GnRH agonist on basal concentrations of serum testosterone and peak values of serum testosterone after administration of hCG was determined. One group of adult male monkeys was treated with a low dose (5-10 micrograms/day) and a second group with a high dose (25 micrograms/day) of a GnRH agonist for 44 weeks. Basal and peak testosterone concentrations were both significantly reduced by GnRH agonist treatment in all groups compared to untreated control animals, but the % rise in serum testosterone above basal values in response to hCG administration was unchanged by agonist treatment. In Exp. 2, the GnRH agonist (100 or 400 ng) or a GnRH antagonist (4 micrograms) was infused into the testicular arteries of adult monkeys. The agonist did not alter testosterone concentrations in the testicular vein or testosterone and LH values in the femoral vein. In Exp. 3, testicular interstitial cells from monkeys were incubated with three concentrations (10(-9), 10(-7) and 10(-5)M) of the GnRH agonist or a GnRH antagonist with and without hCG. After 24 h, neither basal nor hCG-stimulated testosterone production was affected by the presence of the GnRH agonist or antagonist. The results from all 3 experiments clearly suggest that GnRH agonist treatment does not directly alter steroid production by the monkey testis.     

Effect of clomiphene citrate on pituitary responsiveness to gonadotropin releasing hormone in rams and wethers

The objective of this study was to determine the effect of clomiphene citrate (clomid) on pituitary responsiveness to gonadotropin releasing hormone (GnRH) in rams and wethers. Doses of 200 mg clomid per ram and 1 mug GnRH per 50 kg body weight were used in studies on 12 rams and 4 wethers. The experimental design involved bleeding each animal at 15-minute intervals for 6.5 hours. At the end of the first hour, GnRH was injected IV. The second GnRH challenge was administered 0.5 hours after an injection of clomid or vehicle (4.5% sorbitol solution) which was given on the third hour. The relative response to clomid or vehicle was calculated as the mean increase in concentration of LH during the two-hour period after the second GnRH injection. Each treatment (clomid and vehicle) was given to all animals with a 14-day recovery period between treatment days. The relative response for the rams receiving vehicle (1.80 +/- 0.65) was greater (P < 0.05) than the response during clomid treatment (0.34 +/- 0.22). This suppression of LH response by clomid was observed in 10 of the 12 rams. In contrast to the rams, the concentrations of LH in wethers after the second GnRH injection were lower than those observed after the first GnRH injection. Similar to the rams, the relative response following clomid treatment of wethers (0.04 +/- 0.04) was less than the relative response (P > 0.05) following vehicle (0.40 +/- 0.16). The results suggest that clomid at this dosage inhibits GnRH-induced release of LH from the pituitary of rams but not of wethers.     

Evidence that testosterone and follicular fluid do not interact in the control of FSH secretion in rams

The hypothesis that testosterone and inhibin interact in the control of FSH secretion in rams was tested. Adult rams were castrated and were simultaneously given testosterone implants and 3-times daily sc injections of 0, 0.4, 0.8 or 1.6 ml charcoal-treated bovine follicular fluid (bFF). After 1 wk, the implants were removed, and the bFF injections continued as before. Blood samples were taken daily for mean LH, FSH and testosterone concentrations, and every 10 min for 12 h in the presence and in the absence of testosterone for assessment of pulsatile LH release. The bFF specifically inhibited FSH secretion from rat pituitary cells in culture. In the presence of testosterone, there were no main effects of bFF on mean plasma FSH or LH concentrations, nor were these values different from their pre-treatment means (P>0.05). Treatment with bFF did not affect LH pulse frequency or amplitude, but the number of rams showing LH pulses was reduced in the 0.8 and 1.6-ml dose groups (P<0.05). Removal of testosterone increased (P<0.05) both gonadotropins. In the absence of testosterone, no main effect of bFF on mean LH or FSH concentrations was observed, although the 1.6-ml dose suppressed the postcastration rise of both LH and FSH. These data suggest that inhibin does not interact with testosterone and that a physiological level of testosterone is sufficient for the regulation of FSH secretion in adult rams.     

Effects of testosterone, dihydrotestosterone and estradiol on gonadotropin release after gonadotropin releasing hormone administration in cyclic mares

Sixteen intact cyclic mares were treated on the fourth day of estrus and then every other day for a total of six injections with 1) testosterone propionate, 2) dihydrotestosterone (DHT) benzoate, 3) estradiol (E2) benzoate or 4) safflower oil. Mares were given gonadotropin releasing hormone (GnRH) on Day 3 of estrus (pretreatment) and again 24 h after the last steroid or oil injection. Treatment with testosterone propionate resulted in a greater (P less than 0.05) follicle-stimulating hormone (FSH) response to the second injection of GnRH compared with all other treatments. Treatment with DHT benzoate also resulted in greater (P less than 0.05) FSH response to GnRH compared with control and E2 benzoate-treated mares. Testosterone propionate and E2 benzoate administration suppressed (P less than 0.05) the normal diestrous rise in FSH concentrations exhibited by the control and DHT benzoate-treated mares. Steroid treatment did not affect the luteinizing hormone (LH) response to GnRH, although testosterone propionate treatment did suppress concentrations of LH in daily blood samples during Days 3 to 6 of treatment. It is concluded that testosterone's effect on FSH after GnRH treatment observed in this and previous experiments can be attributed to two different properties of the hormone or its metabolites acting simultaneously. That is, testosterone increased the secretion of FSH in response to GnRH as did DHT (an androgenic effect). At the same time, testosterone suppressed FSH concentrations in daily blood samples in a manner identical to that of E2 benzoate (an estrogenic effect).     

Antagonistic and agonistic GnRH analogue treatment of precocious puberty: tracking gonadotropin concentrations in urine

BACKGROUND: The pharmacodynamics of gonadotropin-releasing hormone (GnRH) agonists includes an initial 'flare-up' of the pituitary-gonadal axis, followed by reduced luteinizing hormone (LH) secretion. The question is if combining a short-acting antagonist with a long-acting agonist can diminish gonadotropin flare-up. METHODS: To achieve quick downregulation in patients with recently diagnosed central precocious puberty (CPP, 7 patients) or short stature with short predicted final height (3 patients), we combined the GnRH antagonist cetrorelix (3 subcutaneous injections every 72 h) at the beginning of GnRH agonist treatment (leuprorelin or triptorelin) in 6 patients and compared the effect to 4 patients treated solely with GnRH agonist. To monitor effects, we measured LH and FSH concentrations in urine collected from initial morning urination during the first month of treatment. RESULTS: In both treatment groups, gonadotropin flare-up could be detected in urine levels increased due to the flare-up phenomenon which was of short duration (<5 days) in the majority (5 of 6) of combined-treated patients and in the minority (1 of 4) of patients treated by agonist alone. During the first 10 days of treatment, mean LH concentration measured in urine was significantly lower in 4 CPP patients treated by the combined therapy compared to 3 CPP patients treated by the agonist only (mean LH combined therapy: 10.4 +/- 2.8 vs. 20.1 +/- 11.0 mU/ml in the agonist-only group, mean +/- SEM, p < 0.05). Significant correlations between stimulated serum LH in GnRH test prior to treatment and maximum urine LH after initiating GnRH analogue treatment (r = 0.547, p = 0.043), as well as basal serum LH and basal urine LH (r = 0.685, p = 0.014) were found. CONCLUSION: Combined GnRH agonist and antagonist treatment led to rapid gonadotropin suppression. Also, urine measurements of LH and FSH seemed suitable for monitoring gonadotropin-inhibiting or -stimulating properties of GnRH analogues in individual patients. However, a controlled trial of a larger patient cohort is required to decide which treatment is the most effective.     

Effects of intermittent pulsatile infusion of luteinizing hormone-releasing hormone on dihydrotestosterone-suppressed gonadotropin secretion in castrate rams

The feedback effects of dihydrotestosterone (DHT) on gonadotropin secretion in rams were investigated using DHT-implanted castrate rams (wethers) infused with intermittent pulsatile luteinizing hormone-releasing hormone (LHRH) for 14 days. Castration, as anticipated, reduced both serum testosterone and DHT but elevated serum LH and follicle-stimulating hormone (FSH). Dihydrotestosterone implants raised serum DHT in wethers to intact ram levels and blocked the LH and FSH response to castration. The secretory profile of these individuals failed to show an endogenous LH pulse during any of the scheduled blood sampling periods, but a small LH pulse was observed following a 5-ng/kg LHRH challenge injection. Dihydrotestosterone-implanted wethers given repeated LHRH injections beginning at the time of castration increased serum FSH and yielded LH pulses that were temporally coupled to exogenous LHRH administration. While the frequency of these secretory episodes was comparable to that observed for castrates, amplitudes of the induced LH pulses were blunted relative to those observed for similarly infused, testosterone-implanted castrates. Dihydrotestosterone was also shown to inhibit LH and FSH secretion and serum testosterone concentrations in intact rams. In summary, it appears that DHT may normally participate in feedback regulation of LH and FSH secretion in rams. These data suggest androgen feedback is regulated by deceleration of the hypothalamic LHRH pulse generator and direct actions at the level of the adenohypophysis.     

Reproductive and endocrine function in rams exposed to the organochlorine pesticides lindane and pentachlorophenol from conception.

There is controversy over the potential endocrine modulating influence of pesticides, particularly during sensitive phases of development. In this study, ram lambs were exposed to lindane and pentachlorophenol from conception to necropsy at 28 weeks of age. The rams (and their mothers) were given untreated feed (n = 7) or feed treated with 1 mg kg-1 body weight per day of lindane (n = 12) or pentachlorophenol (n = 5). Semen was collected from 19 weeks onwards and reproductive behaviour was tested at 26 weeks. Serum was collected every 2 weeks and at 27 weeks every 15 min for 6 h during both day and night, and for 1 h before and 5 h after stimulation with GnRH, adrenocorticotrophic hormone and thyroid-stimulating hormone. The pesticides did not affect body weight and ejaculate characteristics, or cause overt toxicity. In pentachlorophenol-treated rams, scrotal circumference was increased. However, seminiferous tubule atrophy was more severe and epididymal sperm density was reduced in comparison with untreated rams at necropsy (P < 0.05). Thyroxine concentrations were lower in pentachlorophenol-treated rams than in untreated rams (P < 0.05). However, after thyroid-stimulating hormone treatment, the thyroxine response was unaltered. Reproductive behaviour was reduced in lindane-treated rams compared with control rams (P < 0.05). Serum LH and oestradiol concentrations during reproductive development, LH pulse frequency at 27 weeks and testosterone secretion after GnRH treatment were lower in lindane-treated rams than in untreated rams (P < 0.05). In summary, the effects of pentachlorophenol on the testis may be linked to a decrease in thyroxine concentrations, and reduced reproductive behaviour in lindane-treated rams may be related to decreased LH, oestradiol and testosterone concentrations.     

Changes in pulsatile LH secretion and the positive and negative feedback actions of oestradiol after administration of a GnRH agonist in the ovariectomized ewe

Administration of a GnRH agonist (5 micrograms) every 12 h to long-term ovariectomized ewes for 5 or 10 days during the breeding season suppressed mean LH levels from around 6 to 1 ng/ml on Days 1 and 4 after treatment; on Day 1 after treatment LH pulse frequency and amplitude were lower than pretreatment values. On Day 4 after treatment LH pulse frequency was restored to pretreatment levels (1 per h) whereas LH pulse amplitude had only slightly increased from 0.5 to 1 ng/ml, a value 25% of that before treatment. This increase in amplitude was greater the shorter the duration of treatment. Ovariectomized ewes treated with the agonist for 5 days exhibited both negative and positive feedback actions after implantation of a capsule containing oestradiol; however, compared to control ewes treated with oestradiol only, the positive and negative feedback actions of oestradiol were blunted. These results suggest that the recovery of tonic LH concentrations after GnRH agonist-induced suppression is limited primarily by changes in LH pulse amplitude. The results also demonstrate that the feedback actions of oestradiol are attenuated, but not blocked, by GnRH agonist treatment.