Evidence for the involvement of central conversion of testosterone to oestradiol-17β in the regulation of luteinizing hormone secretion in the cockerel

1983 ◽  
Vol 99 (2) ◽  
pp. 301-310 ◽  
Author(s):  
S. C. Wilson ◽  
P. G. Knight ◽  
F. J. Cunningham

Treatment of intact cockerels with the synthetic antioestrogen tamoxifen caused a significant increase in the plasma concentration of LH. In contrast, passive immunization with an antiserum raised against oestradiol-17β did not lead to an increase in plasma LH. A pronounced depressive effect of injections of 0·1 mg testosterone propionate (TP) or 0·1 mg oestradiol benzoate (OB) on plasma concentrations of LH was prevented by tamoxifen. Furthermore, a pronounced rise in the concentration of LH releasing hormone in the posterior hypothalamus after the injection of cockerels with OB was completely inhibited by tamoxifen. Neither 0·1 nor 0·5 mg androstenedione modified the concentration of LH in plasma. A dose of 0·05 mg TP, which failed to depress the concentration of LH in plasma of intact cockerels, caused a marked fall in plasma LH in castrated cockerels. Tamoxifen itself exhibited weak oestrogen agonist activity in castrated cockerels by causing a reduction in the concentration of LH in plasma. However, tamoxifen prevented any further depressive effect on LH resulting from the injection of TP. These findings suggest that testosterone exerts an inhibitory influence on LH secretion at the central neural level, partially at least, by means of the product of its aromatization, oestradiol-17β.

1977 ◽  
Vol 84 (1) ◽  
pp. 45-50 ◽  
Author(s):  
E. V. YoungLai

ABSTRACT Experiments were performed in the rabbit to determine whether 20α-hydroxy-4-pregnen-3-one (20-OHP) can maintain luteinizing hormone (LH) secretion after injections of LH-releasing hormone (LH-RH). Female rabbits were castrated at least 2 weeks prior to investigation. On the day before LH-RH injection they were cannulated and a dose of oestradiol benzoate (OeB), 100 μg/kg, given intramuscularly. LH-RH, 500 ng/kg, was injected as a bolus via the cannula and 20-OHP, 100 μg/kg and 2.5 mg/kg, injected intramuscularly immediately after. Blood was withdrawn at intervals for up to 5½ h after LH-RH injection. LH secretion dropped to pre-stimulation levels within 3 h after LH-RH alone or in combination with 20-OHP. Administration of LH-RH to oestrogen primed intact females also gave a peak of LH which returned to pre-stimulation levels within 3 h. However, mating seemed to maintain LH levels for a greater period of time.


Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4558-4564 ◽  
Author(s):  
Gregory A. Dissen ◽  
Robert K. Dearth ◽  
H. Morgan Scott ◽  
Sergio R. Ojeda ◽  
W. Les Dees

Abstract We determined whether the effect of alcohol (ALC) to suppress LH secretion in immature female monkeys is due to a hypothalamic or pituitary site of action. Beginning at 20 months of age, four monkeys received a single intragastric dose of ALC (2.4 g/kg), and four monkeys received an equal volume of a saline/sucrose solution daily until they were 36 months old. For the hypothalamic response test, two basal samples (3.5 ml) were collected at 15-min intervals via the saphenous vein, and then N-methyl-d-l-aspartic acid (NMA; 20 mg/kg) was given iv and four more blood samples collected. Three weeks later, this protocol was repeated except LH-releasing hormone (LHRH) (5 μg/kg) was used to test pituitary responsiveness. NMA or LHRH was administered 3 h after the ALC. After the pituitary challenge, each monkey was ovariectomized and 6 wk later, implanted with an indwelling subclavian vein catheter. Blood samples were drawn every 10 min for 8 h to assess effects of ALC on post-ovariectomy LH levels and the profile of LH pulsatile secretion. The hypothalamic challenge showed NMA stimulated LH release in control monkeys, an action that was blocked by ALC. The pituitary challenge revealed that LHRH stimulated LH release equally well in control and ALC-treated monkeys. A post-ovariectomy rise in LH was observed in both groups, but levels were 45% lower in ALC-treated monkeys. This reduction was attributed to an ALC-induced suppression of both baseline and amplitude of pulses. Results demonstrate that the ALC-induced suppression of LH in immature female rhesus monkeys is due to an inhibitory action of the drug at the hypothalamic level.


1977 ◽  
Vol 75 (2) ◽  
pp. 251-260 ◽  
Author(s):  
G. CHAZAL ◽  
M. FAUDON ◽  
F. GOGAN ◽  
M. HERY ◽  
C. KORDON ◽  
...  

Implantation of a solid source of oestradiol into ovariectomized rats produced constant plasma concentrations of the hormone over a long period of time. Under these conditions, LH is released in a circadian pattern with a very marked peak in the afternoon. This circadian rhythm is synchronized to the light–darkness cycle, since it follows exactly a shift in the nycthemeral cycle. The first peak appeared on day 3 after placement of the oestrogen implant; its amplitude was constant from days 3 to 9 after implantation, and decreased gradually during prolonged implantation. The afternoon peak was not correlated with changes in the pituitary sensitivity to exogenous LH releasing hormone (LH-RH), since the LH response to increasing doses of the peptide could be superimposed in the morning and in the afternoon. However, the decreased amplitude of the rhythm observed after more than 9 days of implantation seemed to depend upon a progressive desensitization of the pituitary gland to LH-RH. Pituitary LH content also decreased as a function of implantation time. It is concluded that, under conditions of constant plasma oestradiol concentrations and of constant pituitary sensitivity to LH-RH, a daily activation of the neural trigger releasing pituitary gonadotrophins occurs.


1981 ◽  
Vol 88 (3) ◽  
pp. 393-400 ◽  
Author(s):  
B. D. SCHANBACHER

An experiment was conducted to determine the importance of episodic LH secretion during pubertal development in beef bulls. Testicular growth, LH secretory patterns and serum testosterone concentrations were monitored in control bulls, and bulls implanted with one or two oestradiol-filled capsules from 26 to 38 weeks of age. Control but not oestradiol-treated bulls showed normal testicular growth and episodic LH secretory patterns. Serum LH and testosterone responses of 38-week-old control and oestradiol-treated bulls to an intravenous challenge of 5 μg LH releasing hormone indicated normal pituitary responsiveness, but steroidogenic responsiveness had not yet developed in oestradiol-treated bulls. Removal of the capsules at 38 weeks of age resulted in a normal episodic release pattern for LH, with concomitant growth of the underdeveloped testes up to 44 weeks of age. Serum concentrations of LH and testosterone were within the range of normal, adult values by 42 weeks of age. These results suggest that oestradiol can interfere with episodic LH secretion and normal pubertal development in beef bulls, and furthermore that episodic LH secretion is commensurate with the establishment of normal development of the bovine testis during puberty.


1978 ◽  
Vol 78 (3) ◽  
pp. 329-342 ◽  
Author(s):  
F. ELSAESSER ◽  
N. PARVIZI ◽  
F. ELLENDORFF

The effects of gonadal secretions on the release of LH and the stimulation of LH secretion by oestradiol have been investigated in newborn male and female miniature pigs; the differences in the feedback action of testosterone in newborn and pubertal male pigs were also studied. Hemi-orchidectomy or orchidectomy of 1-week-old pigs had no effect on the level of LH in the plasma; total orchidectomy significantly reduced the levels of testosterone (P<0·01) and progesterone (P<0·05). In female pigs ovariectomized at 1 week of age, the concentration of LH in the plasma decreased, with a strong negative correlation between the level of LH and age (r = −0·41; P < 0·05). The plasma concentration of progesterone was generally low and unaffected by ovariectomy. Orchidectomy and treatment of male pigs, at 1 week of age, with testosterone (6 mg/kg body weight) had no effect on the plasma concentration of testosterone 24 h after treatment. If testosterone propionate was given rather than testosterone, the level of LH was significantly reduced (P< 0·001) 24 h after the injection and the concentration of testosterone in the plasma corresponded to that found in the intact adult male pig. Treatment with oestradiol or oestradiol benzoate did not affect the concentration of LH. Orchidectomy and treatment of pubertal male pigs with testosterone propionate resulted in a significantly (P < 0·001) higher concentration of testosterone in the plasma, compared with newborn pigs treated similarly, but the level of LH was unchanged. This suggests that there is a more rapid rate of clearance of testosterone in the newborn than in the pubertal male miniature pig and that the negative feedback of testosterone is not mediated by aromatization in the newborn animal and it declines before or during puberty. Treatment of newborn intact male and female and gonadectomized male pigs with oestradiol benzoate produced similar variations in the plasma level of oestradiol in all groups of animals. In the female pigs, however, a surge-like release of LH was observed 60–72 h after the injection of oestradiol benzoate, suggesting that the stimulatory feedback mechanism can operate soon after birth and that the response is sexually dimorphic.


1990 ◽  
Vol 125 (1) ◽  
pp. 139-146 ◽  
Author(s):  
S. C. Wilson ◽  
R. T. Gladwell ◽  
F. J. Cunningham

ABSTRACT Changes in the hypothalamic contents of LHRH-I and LHRH-II were determined in intact and castrated cockerels injected i.m. with gonadal steroids or tamoxifen. An increase in the plasma concentration of LH after castration was accompanied by a significant increase in the content of LHRH-I in the posterior hypothalamus (including the mediobasal hypothalamus and median eminence) which was reversed by oestradiol benzoate given on days 14 and 15 after castration. Under similar circumstances, testosterone propionate did not modify the hypothalamic content of LHRH-I, even though both steroids reduced the plasma concentrations of LH to levels below those of intact cockerels. Treatment of intact cockerels with oestradiol benzoate significantly increased the content of LHRH-I in the posterior hypothalamus, whilst testosterone propionate was again without effect. Tamoxifen significantly raised the plasma concentration of LH in intact cockerels and partially antagonized the suppressive effect of oestradiol benzoate and testosterone on LH secretion in castrated cockerels. However, an anti-oestrogenic effect of tamoxifen on the hypothalamic content of LHRH-I was not demonstrated. There was no evidence of any changes in the hypothalamic content of LHRH-II after castration, with or without gonadal steroid replacement. A change in the hypothalamic content of LHRH-I in response to manipulation of the steroid environment would imply an involvement of this peptide in the mechanism by which gonadal steroids regulate the release of LH. The absence of changes in the hypothalamic content of LHRH-II in the same circumstances suggest that it is not directly involved in the control of LH secretion by the gonadal steroid negative feedback loop. Journal of Endocrinology (1990) 125, 139–146


1982 ◽  
Vol 92 (3) ◽  
pp. 389-395 ◽  
Author(s):  
TAKASHI HIGUCHI ◽  
MASAZUMI KAWAKAMI

Ovariectomized rats with neural deafferentation at the level of the posterior border of the anterior hypothalamic area (AC rats) were used to re-evaluate the direct feedback effect of oestrogen on the regulation of LH secretion by the pituitary gland. Synthetic LH releasing hormone (LH-RH; 300 ng/kg), injected at 30-min intervals into AC rats with undetectable basal LH, induced pulsatile increase of serum LH concentrations. Oestradiol-17β (5 μg), administered i.v. just before the first LH-RH injection, significantly decreased the LH response to a second injection of LH-RH given 30 min later and to subsequent injections. Maximal inhibition was 58%. Oestradiol-17β (5 μg) given i.v. to control ovariectomized rats decreased serum LH concentrations 40 min after administration; the maximum reduction being 52%. An s.c. injection of oestradiol benzoate (5 μg) increased pituitary responsiveness to LH-RH by the next day in AC rats but decreased serum LH levels in control ovariectomized rats. These results indicate that acute inhibitory and chronic facilitatory effects of oestrogen on LH secretion are exerted at the pituitary gland, without a change in LH-RH secretion. The prolonged inhibitory effect of oestrogen is at the level of the hypothalamus and causes a reduction in LH-RH secretion.


1983 ◽  
Vol 102 (4) ◽  
pp. 499-504 ◽  
Author(s):  
M. J. D'Occhio ◽  
B. D. Schanbacher ◽  
J. E. Kinder

Abstract. The acute castrate ram (wether) was used as an experimental model to investigate the site(s) of feedback on luteinizing hormone (LH) by testosterone, dihydrotestosterone and oestradiol. At the time of castration, wethers were implanted subdermally with Silastic capsules containing either crystalline testosterone (three 30 cm capsules), dihydrotestosterone (five 30 cm capsules) or oestradiol (one 6.5 cm capsule). Blood samples were taken at 10 min intervals for 6 h 2 weeks after implantation to determine serum steroid concentrations and to characterize the patterns of LH secretion. Pituitary LH response to exogenous LRH (5 ng/kg body weight) were also determined at the same time. The steroid implants produced serum concentrations of the respective hormones which were either one-third (testosterone) or two-to-four times (dihydrotestosterone, oestradiol) the levels measured in rams at the time of castration. Non-implanted wethers showed rhythmic pulses of LH (pulse interval 40–60 min) and had elevated LH levels (16.1 ± 1.6 ng/ml; mean ± se) 2 weeks after castration. All three steroids suppressed pulsatile LH release and reduced mean LH levels (to below 3 ng/ml) and pituitary LH responses to LRH. Inhibition of pulsatile LH secretion by all three steroids indicated that testosterone as well as its androgenic and oestrogenic metabolites can inhibit the LRH pulse generator in the hypothalamus. Additional feedback on the pituitary was indicated by the dampened LH responses to exogenous LRH.


1996 ◽  
Vol 135 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Joaquin Lado-Abeal ◽  
Jose L Liz ◽  
Carlos Rey ◽  
Manuel Febrero ◽  
Jose Cabezas-Cerrato

Lado-Abeal J, Liz JL, Rey C, Febrero M, Cabezas-Cerrato J. Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women. Eur J Endocrinol 1996;135:293–8. ISSN 0804–4643 It is well established that valproate increases hypothalamic concentrations of γ-aminobutyric acid (GABA). Although little research has been done on the role of GABA in the control of pulsatile luteinizing hormone (LH) secretion in humans, our group recently found that administration of valproate had no significant effect on pulsatile LH secretion in late follicular and mid-late luteal phase normal women. However, the results of several studies of rats suggest that GABAergic regulation of LH secretion may depend on steroid levels. The objective of this work was to determine whether regular administration of sodium valproate inhibits pulsatile LH secretion in ovariectomized women. Twelve women who had undergone ovariectomy for causes other than malignant tumors were each studied in two 8 h sessions, in each of which blood samples were taken every 5 min. The first session was the control; for the second, 400 mg of sodium valproate was administered every 8 h during the seven preceding days and at 08.00 h and 14.00 h on the day of the study session. Serum valproate was determined by repolarization fluorescence spectrophotometry, and LH, estradiol and progesterone by radioimmunoassay. The serum LH series were subjected to a deconvolution procedure to reconstruct the pattern of pituitary LH secretion. Luteinizing hormone pulses were identified by the authors' nonparametric method. Control and post-valproate results were compared with regard to number of pulses, pulse duration, the quantity of LH secreted in each pulse, interpulse interval and mean serum LH level. There was no statistically significant difference between control and post-valproate results for any of the variables considered. It is concluded that sustained serum valproate levels do not alter pulsatile secretion of LH in ovariectomized women. This implies that, in humans, GABA is probably not a decisive factor in the regulation of the GnRH pulse generator. J Cabezas-Cerrato, Endocrinology and Nutrition Service, General Hospital of Galicia, c/Galeras s/n 15705, Santiago de Compostela, La Coruña, Spain


1986 ◽  
Vol 109 (2) ◽  
pp. 169-174 ◽  
Author(s):  
J. N. Hugues ◽  
A. Enjalbert ◽  
E. Moyse ◽  
C. Shu ◽  
M. J. Voirol ◽  
...  

ABSTRACT The role of somatostatin (SRIF) on adenohypophysial hormone secretion in starved rats was reassessed by passive immunization. Because of the absence of pulsatile GH secretion in starved rats, the effects of the injection of SRIF antiserum on GH levels can be clearly demonstrated. To determine whether starvation modifies the sensitivity of the adenohypophysis to SRIF, we measured 125I-labelled iodo-N-Tyr-SRIF binding. There was no difference in the dissociation constant (Kd) nor in the maximal binding capacity (Bmax) in fed (n = 15) and starved (n = 15) animals (Kd = 0·38 ± 0·09 (s.e.m.) and 0·45 ± 0·09 nmol; Bmax = 204 ± 39 and 205 ± 30 fmol/mg protein respectively). Administration of SRIF antiserum resulted in a dose-dependent increase in plasma concentrations of GH, TSH and prolactin. The minimal effective dose of SRIF antiserum was 50 μl for GH, 100 μl for TSH and 200 μl for prolactin. Our results show that: (1) starvation does not modify adenohypophysial SRIF-binding sites, (2) in starved male rats endogenous SRIF exerts a negative control on prolactin secretion in vivo and (3) sensitivity to endogenous SRIF seems to be different for each hypophysial cell type. J. Endocr. (1986) 109, 169–174


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