Testosterone maintains pituitary and serum FSH and spermatogenesis in gonadotrophin-releasing hormone antagonist-suppressed rats

1986 ◽  
Vol 108 (1) ◽  
pp. 101-107 ◽  
Author(s):  
M. A. Rea ◽  
G. R. Marshall ◽  
G. F. Weinbauer ◽  
E. Nieschlag
Keyword(s):  
Serum Testosterone ◽  
Treated Group ◽  
Male Rats ◽  
Testis Weight ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Hypophysectomized Rats ◽  
Gonadotrophin Releasing Hormone ◽  
Vehicle Treated Control

ABSTRACT Groups of adult male rats were treated continuously for 30 days with either vehicle or the potent gonadotrophin-releasing hormone (GnRH) antagonist, (N-Ac-d-Nal(2)1,d-pCl-Phe2,d-Trp3,d-hArg (Et2)6,d-Ala10)-GnRH (RS 68439; 35 μg/day). In addition, groups of vehicle- and antagonist-treated rats received s.c. testosterone implants sufficient to maintain serum testosterone concentrations 3·5- to 5-fold higher than those of vehicle-treated control rats. After 30 days of antagonist treatment serum LH, FSH and testosterone concentrations were at or below the detection limits of their respective assays and pituitary FSH content and GnRH receptor binding were reduced, relative to control animals, by 77 and 98% respectively. Testis weight in antagonist-treated rats was reduced by 75% and spermatogenesis was suppressed to an extent comparable to that observed in hypophysectomized rats. Testosterone, which caused a 40% reduction in serum FSH relative to control animals, prevented the antagonist-induced fall in both serum and pituitary FSH, but not GnRH receptors, below that observed in the vehicle plus testosterone-treated group. Furthermore, spermatogenesis in the antagonist plus testosterone-treated group was indistinguishable from that observed in control animals. It is concluded that testosterone is capable of maintaining serum and pituitary FSH levels in vivo, under conditions which presumably render the pituitary insensitive to hypothalamic GnRH. J. Endocr. (1986) 108, 101–107

ANTERIOR PITUITARY SENSITIVITY IN IMMATURE FEMALE RATS STIMULATED WITH GONADOTROPHIN RELEASING HORMONE IN VIVO: EFFECT OF PRIMING WITH OESTROGEN, PREGNANT MARE SERUM GONADOTROPHIN OR BRAIN LESION

1977 ◽  
Vol 74 (1) ◽  
pp. 99-109 ◽  
Author(s):  
D. DE ZIEGLER ◽  
M. WILKINSON ◽  
DANIELLE CASSARD ◽  
K. B. RUF
Keyword(s):  
Brain Lesion ◽  
Treated Group ◽  
Female Rats ◽  
Similar Degree ◽  
Female Rat ◽  
Immature Female ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Pregnant Mare Serum Gonadotrophin

An investigation of pituitary sensitivity, assessed in terms of increments in plasma LH and FSH concentrations, to stimulation with one or two injections of gonadotrophin releasing hormone (GnRH) was carried out on 26-day-old immature female rats which had received one of the following priming treatments: 10 μg oestradiol benzoate (OB) as a single injection on day 23 or day 25, or on both days; 10 i.u. pregnant mare serum gonadotrophin (PMSG) on day 24; an electrochemical brain lesion placed in the mediobasal hypothalamus on day 23; control animals received either vehicle alone or a sham lesion. Pituitary sensitivity assessed at 10.00 h on day 26, after one or two injections of GnRH (100 ng/100 g body weight, s.c.), was enhanced to a similar degree in the three groups treated with OB in terms of LH (P < 0-01). The FSH response also increased after OB treatment but was not statistically significant. In contrast, 48 h after the injection of PMSG (i.e. when the rats were in a 'pro-oestrous-like' condition) pituitary sensitivity in terms of both LH and FSH dropped sharply (P < 0·001). In lesioned animals, pituitary sensitivity to one injection of GnRH was unchanged. A second GnRH injection administered after a 60 min interval induced a slightly larger LH response in control animals. In contrast, the ratio of the second response to the first increased in animals treated with PMSG, despite the state of overall decrease in sensitivity, being 4·5:1 in PMSG-treated rats versus 1·4:1 in controls. In a second set of experiments, we investigated the variation of pituitary sensitivity in conjunction with an experimentally induced gonadotrophin surge. In animals treated with OB on day 23 and with 1 mg progesterone at 12·00 h on day 26, pituitary sensitivity was increased at both 14.00 and 17.00 h as compared with that in the day 23 OB-treated group at 10.00 h. The PMSG-treated animals maintained their state of decreased responsiveness at 14.00 h, but exhibited increased pituitary sensitivity at the time of the gonadotrophin surge (17.00 h). These results show that OB increases pituitary sensitivity to GnRH in 26-day-old female rats and that the induction of a gonadotrophin surge further increases this sensitivity. In contrast, PMSG-treated rats displayed a state of decreased responsiveness 48 and 52 h, but not 55 h, after the injection. Pituitary sensitivity on the second day after PMSG treatment thus clearly differs from that observed during pro-oestrus in the adult cyclic female rat.

Acute and short-term actions of serotonin administration on the pituitary-testicular axis in the adult rat

1995 ◽  
Vol 7 (5) ◽  
pp. 1101 ◽  
Author(s):  
MP Hedger ◽  
S Khatab ◽  
G Gonzales ◽  
Kretser DM de
Keyword(s):  
Serum Testosterone ◽  
Fold Increase ◽  
Significant Inhibition ◽  
Male Rats ◽  
Minor Role ◽  
Testis Weight ◽  
Serum Concentrations ◽  
Adult Rat ◽  
Serum Lh ◽  
A Minor

In this study, adult male rats were injected intraperitoneally with a single dose of serotonin (5-hydroxytryptamine, 5HT; 10 mg kg-1 bodyweight) for 2 h or 18 h, or daily with graded doses of 5HT (0.1-10 mg kg-1) for four days before being killed. Serum and testicular interstitial fluid (IF) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and immunoreactive-inhibin were measured by radioimmunoassay, and one testis was removed for histological examination. At 2 h after a single injection, 5HT caused a significant inhibition of serum concentrations of LH and inhibin, recovered IF volume and intratesticular testosterone concentrations; testis weight and serum concentrations of testosterone and FSH were unaffected. At 18 h after injection, all parameters had returned to normal, with the exception of intratesticular testosterone concentration which remained lower than normal. The lowest 5HT dose (0.1 mg kg-1) had no effect on any parameter following four daily injections. At a dose of 1.0 mg kg-1 5HT, there was a four-fold increase in the concentration of serum LH, but testis weight, recovered IF volume, testosterone and inhibin concentrations and serum concentrations of FSH were not significantly affected. At the highest dose of 5HT (10 mg kg-1) after four daily injections, testis weight decreased, and IF volume increased nearly three-fold. Testis concentrations of inhibin and serum testosterone were reduced, whereas serum concentrations of both LH and FSH were elevated; intratesticular testosterone concentrations did not differ from controls. Only at the highest dose of 5HT was disruption to the seminiferous epithelium observed, with focal damage ranging in severity from increased degeneration of spermatogenic cell profiles, to complete loss of the germinal epithelium; however, many tubule profiles displayed completely normal spermatogenesis. The acute IF volume reduction and spermatogenic disruption in 5HT-treated rats were consistent with localized ischaemia due to constriction of the testicular arterial supply. The eventual increase in IF volume observed after 5HT treatment appeared to be secondary to the loss of germ cells. Although 5HT also inhibited pituitary LH release and Leydig cell steroidogenesis, these effects appeared to play only a minor role in the induction of spermatogenic damage.

HYPOTHALAMIC-PITUITARY-TESTICULAR SYSTEM FOLLOWING TESTICULAR X-IRRADIATION

1976 ◽  
Vol 83 (1) ◽  
pp. 190-200 ◽  
Author(s):  
H. L. Verjans ◽  
K. B. Eik-Nes
Keyword(s):  
Interstitial Cell ◽  
Serum Testosterone ◽  
Male Rats ◽  
Ventral Prostate ◽  
Testis Weight ◽  
X Ray ◽  
Serum Lh ◽  
Testicular Weight ◽  
Unknown Factor ◽  
X Irradiation

ABSTRACT Testes of adult, male rats were exposed to a total dose of 1500 R of X-irradiation. Testicular weight decreased from day 8 after X-ray treatment. This decrease was, however, preceded by an increment of the testis weight on day 4 following treatment. X-ray treatment of testes was associated with significant increases in serum FSH. Testicular irradiation had, however, no effect on ventral prostate and seminal vesicles weights. Serum testosterone increased only on day 1, 2 and 4 after irradiation, while serum LH levels tended to increase from day 8 post-irradiation. These changes were not significant, however, when compared with non-irradiated controls. At 7, 13 and 20 days following 1500 R of bilateral, testicular X-irradiation, the hypothalamic-pituitary unit was still capable of responding to exogenous gonadotrophin releasing factor. Serum FSH may in male rats be regulated at least partly by circulating steroids of testicular origin and partly by an unknown factor of non-interstitial cell nature.

Hyperprolactinaemia attenuates the gonadotrophin releasing hormone receptor response to gonadectomy in rats

1982 ◽  
Vol 95 (2) ◽  
pp. 267-274 ◽  
Author(s):  
R. N. Clayton ◽  
L. C. Bailey
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Serum Prolactin ◽  
Intact Male ◽  
Adult Rats ◽  
Releasing Hormone ◽  
Receptor Response ◽  
Serum Lh ◽  
Gonadotrophin Releasing Hormone ◽  
Qualitative Index

Measurement of pituitary gonadotrophin releasing hormone (Gn-RH) receptor content provides a qualitative index of prior exposure of the pituitary gland to endogenous Gn-RH. The effect of moderate hyperprolactinaemia (serum prolactin = 95–250 μg/l), achieved with three pituitary grafts beneath the renal capsule, on the pituitary Gn-RH receptor content and serum LH responses to gonadectomy of adult rats has been studied. In males the presence of hyperprolactinaemia for 7 days completely prevented the increase in Gn-RH receptor content 3 days after castration and inhibited the serum LH rise by 45%. By 6 days after castration, Gn-RH receptors had increased in the hyperprolactinaemic castrated animals but values were 33% lower than in sham-grafted controls, while the serum LH increase was attenuated by 30%. Pituitary LH content was also lower in grafted castrated animals 6 days after castration. Hyperprolactinaemia for 3 weeks had no effect on Gn-RH receptors or pituitary LH content of intact male rats, although basal serum LH was decreased by 50%. Hyperprolactinaemia also attenuated the increases in Gn-RH receptors, serum LH and pituitary LH which occurred 6 days after ovariectomy in female rats. In all experiments the pituitary content of prolactin was reduced by 80–90% in animals bearing pituitary grafts. These results suggest that hyperprolactinaemia restricts the Gn-RH receptor response to gonadectomy by decreasing endogenous hypothalamic Gn-RH secretion.

Sexual maturation of male rats treated postnatally with a gonadotrophin-releasing hormone antagonist

1988 ◽  
Vol 116 (2) ◽  
pp. 241-246 ◽  
Author(s):  
K.-L. Kolho ◽  
H. Nikula ◽  
I. Huhtaniemi
Keyword(s):  
Sexual Maturation ◽  
Gnrh Antagonist ◽  
Prolactin Receptor ◽  
Male Rats ◽  
Delayed Puberty ◽  
Testis Weight ◽  
Adult Rats ◽  
Releasing Hormone ◽  
Treatment Groups ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Postnatal secretion of gonadotrophin by male rats was inhibited by a potent gonadotrophin-releasing hormone (GnRH) antagonist analogue (N-Ac-4-Cl-d-Phe1,4-Cl-d-Phe2,d-Trp3,d-Phe6,des-Gly10-GnRH-d-alanylamide; Org 30039; 2 mg/kg s.c. twice daily) on days 1–5, 6–10, 11–15 or 16–20 of life. The onset of puberty was determined by monitoring the separation of the preputium from the glans penis, i.e. balanopreputial separation (BPS). Rats treated on days 1–5 matured normally, whereas all treatments between days 6 and 20 delayed BPS (P < 0·01). In adult rats (between 110 and 160 days of age), testis weights were reduced by 21–35% (P < 0·01) in groups treated between days 1 and 15, although weights of the accessory sex glands were normal. Testicular FSH receptors were decreased by 31–47% (P < 0·01) in all treatment groups, whereas the LH receptor content was decreased only in rats treated between days 1 and 5 (18%; P < 0·05) and prolactin receptor content decreased only in rats treated up to day 10 (31–33%; P < 0·01). Concentrations of serum testosterone, LH and FSH, and pituitary contents of LH and FSH were unaffected by neonatal treatment with Org 30039. Animals treated with Org 30039 had reduced fertility which was most pronounced (88%; P < 0·01) in rats treated between days 1 and 5. However, motile sperm were detectable in the cauda epididymis of the infertile rats. In conclusion, postnatal gonadotrophin deprivation induced with a GnRH antagonist for different 5-day periods during the first 15 days of life delayed puberty, reduced adult testis weight and impaired fertility. Some effects of the antagonist were largely independent of the timing of gonadotrophin suppression. Other effects, including suppression of testicular LH and prolactin receptors and the delay in the onset of puberty, were found only in the younger and older treatment groups respectively. These findings emphasize the importance of neonatal hypothalamic-pituitary-gonadal function for subsequent sexual maturation. J. Endocr. (1988) 116, 241–246

Suppression and recovery of pituitary gonadotrophin secretion in intact and orchidectomized rats treated neonatally with a gonadotrophin-releasing hormone antagonist

1989 ◽  
Vol 122 (2) ◽  
pp. 519-526 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi
Keyword(s):  
Gnrh Antagonist ◽  
Recovery Period ◽  
Neonatal Rat ◽  
Male Rats ◽  
Minor Role ◽  
Gnrh Antagonists ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Suppression of neonatal rat pituitary-testis function by gonadotrophin-releasing hormone (GnRH) antagonists results in delayed sexual maturation and infertility. Since the mechanism is not understood, the acute effects of a GnRH antagonist on gonadotrophin secretion in neonatal male rats has been studied in more detail. Treatment with a GnRH antagonist analogue, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(ET2)6,d-Ala10-GnRH (2 mg/kg per day) on days 1–10 of life had prolonged effects on gonadotrophin secretion; serum LH and FSH recovered in 1 week, but the pituitary content took 2 weeks to recover. Likewise, LH and FSH responses to acute in-vivo stimulation with a GnRH agonist were still suppressed 1 week after the treatment. Interestingly, a rebound (86% increase) in basal serum FSH was found 16 days after treatment with the antagonist. Whether testis factors influence gonadotrophin secretion during treatment with the GnRH antagonist and/or in the subsequent recovery period was also assessed. Neonatal rats were castrated on days 1, 5 or 10 of the 10-day period of antagonist treatment. Orchidectomy on days 1 and 5 only marginally affected gonadotrophin secretion. When orchidectomy was performed at the beginning of the recovery period, no effects on pituitary recovery were seen within 1 week of castration. After 16 days, serum LH and FSH in the antagonist-treated and control castrated rats were equally increased but the pituitary contents of the antagonist-treated rats were still suppressed. Finally, the effect of testosterone treatment on the recovery of gonadotrophin secretion after antagonist suppression was studied in intact and orchidectomized animals. The rats were implanted with testosterone capsules for 7 days after treatment with the GnRH antagonist in the neonatal period. Testosterone suppressed pituitary LH contents similarly in all groups of animals, but had no effects on serum LH. Paradoxically, serum FSH was suppressed 50% by testosterone in intact and castrated antagonist-treated rats and in castrated controls but not in intact controls. These findings suggest that suppression of FSH by testosterone is only seen in neonatal animals with low endogenous levels of this androgen, whether due to GnRH antagonist treatment or castration. It is concluded that neonatal treatment with a GnRH antagonist results in prolonged suppression of LH and FSH secretion, that testis factors play only a minor role in pituitary modulation during the antagonist suppression and that more disturbances are observed in the post-treatment recovery of FSH secretion than in that of LH. Journal of Endocrinology (1989) 122, 519–526

TESTICULAR RECEPTORS FOR LUTEINIZING HORMONE AFTER IMMUNONEUTRALIZATION OF GONADOTROPHIN RELEASING HORMONE IN THE MALE RAT

1977 ◽  
Vol 75 (1) ◽  
pp. 23-32 ◽  
Author(s):  
R. L. HAUGER ◽  
R. P. KELCH ◽  
YII-DER IDA CHEN ◽  
ANITA H. PAYNE
Keyword(s):  
Selective Reduction ◽  
Serum Testosterone ◽  
Pituitary Hormones ◽  
Male Rats ◽  
Male Rat ◽  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Intact Male ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone

The effects of immunoneutralization of endogenous gonadotrophin releasing hormone (GnRH) on the serum concentrations of testosterone and gonadotrophins and the binding of 125I-labelled human chorionic gonadotrophin (HCG) to testicular membrane fractions were studied in adult male rats. Four days after the administration of 1 ml anti-GnRH serum, the level of testosterone in the serum decreased to 44% of the concentration before the injection, whereas administration of normal rabbit serum had no effect. Multiple injections of anti-GnRH serum for 4 days dramatically suppressed the secretion of gonadotrophins in rats orchidectomized 2 months earlier. In intact male rats treated identically, immunoneutralization of GnRH decreased the level of serum testosterone to 32% of the concentration present in saline-treated controls, but did not decrease the number of testicular binding sites for HCG (LH). Administration of testosterone or oestradiol for 3 or 6 days caused a marked reduction in the concentration of serum gonadotrophins but did not decrease the number of LH receptors. This study provides further support for the concept that one releasing hormone governs secretion of both FSH and LH. In addition, these studies indicate that selective reduction of gonadotrophins for 3–6 days has no effect on the number of testicular LH receptors. This suggests that pituitary hormones other than gonadotrophins may be important in the maintenance of testicular receptors for LH.

Comparison of oestrogen and GnRH agonist analogue-induced inhibition of the pituitary-testicular function in rat

1983 ◽  
Vol 103 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Ilop T. Huhtaniemi ◽  
Dwight D. Warren ◽  
Kevin J. Catt
Keyword(s):  
Serum Testosterone ◽  
Ventral Prostate ◽  
Testicular Function ◽  
Inhibitory Effects ◽  
Adult Rats ◽  
Serum Progesterone ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Hormone Injection ◽  
Gonadotrophin Releasing Hormone

Abstract. The purpose of the present study was to compare the inhibitory effects of oestrogen and a gonadotrophin releasing hormone agonist analogue (GnRH-A) on the pituitary-testicular function of adult rats. Animals were treated with sc injections of oestrogen (diethylstilboestrol, DES, 5 or 50 μg/kg body weight/day) or a gonadotrophin releasing hormone agonist analogue. [(D-Ser-(tBu)6)des-Gly10-GnRH N-ethylamide, GnRH-A, 0.4 or 4 μg/kg/day] up to 12 days. Serum LH (24 h after the last hormone injection) decreased by 83% in 3 days with DES, but was unchanged during 12 days of GnRH-A treatment. Serum testosterone (T) decreased by 98% during DES treatment, and also clearly but less profoundly, by 89%, with GnRH-A. Maximal decrease in the weights of the ventral prostate and seminal vesicles were 73–78% with DES-treatment, but clearly slower, and to a lesser extent, with GnRH-A (33–41%). Testicular weights decreased consistently (up to 41%) with GnRH-A treatment only. DES decreased the content of testicular LH receptors by 40% in 12 days whereas GnRH-A caused a loss of 97% in LH binding. Testicular lactogen receptors decreased to similar extents (by 68–78%) with both treatments. A clear increase in serum progesterone/T ratio was observed with both types of treatment, suggesting blockade of steroidogenesis at the C21 steroid level. These findings suggest that the antigonadal actions of oestrogen in the intact animal are largely due to a decrease of circulating gonadotrophin levels, and that those of GnRH-A are predominately due to Leydig cell LH-receptor down-regulation and steroidogenic lesions, induced by transiently elevated gonadotrophin levels. The inhibitory effects of oestrogen on testicular function appeared to be faster and more complete that those of GnRH-A in the present short-term experiments.

RESPONSE OF THE PITUITARY-TESTICULAR AXIS TO LUTEINIZING HORMONE-RELEASING HORMONE IN THE IMMATURE MALE RAT

1977 ◽  
Vol 84 (2) ◽  
pp. 254-267 ◽  
Author(s):  
H. Edward Grotjan ◽  
Donald C. Johnson
Keyword(s):  
Luteinizing Hormone ◽  
Control Level ◽  
Serum Testosterone ◽  
Male Rats ◽  
Male Rat ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Immature Male ◽  
Serum Lh ◽  
Lh Rh

ABSTRACT Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and androstenedione were measured by radioimmunoassays in the sera of immature male rats treated with luteinizing hormone-releasing hormone (LH-RH). A single dose of 10, 20, 40 or 80 ng of LH-RH produced a prompt increase in serum LH: significant changes in FSH were found only with the two larger doses. Serum testosterone increased to peak levels in 20 to 40 min and returned to control level by 120 min. Changes in androstenedione were temporally similar but smaller in magnitude. Four doses of 20 or 40 ng LH-RH given at 20 min intervals did not increase serum LH or testosterone concentrations above those found with a single injection; FSH was slightly higher after the fourth dose. However, 40 ng LH-RH given every 20 min for 2 h produced a dramatic increase in serum LH and FSH: serum and testicular androgens were also much higher during the second hour. A 2 h stimulation with 80 ng LH-RH given ip at 30 min intervals did not alter the response to the same treatment given 24 h later; i. e., neither the pituitary nor the gonad was primed by previous exposure to increased levels of LH-RH or gonadotrophins. These results suggest that a single pulse of LH-RH produces a predictable response in the animal, but multiple episodic stimuli produce variable responses: testes, on the other hand, produce androgens as long as gonadotrophins are available.

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