THE EFFECT OF HYPOTHALAMIC STIMULATION AND PROGESTERONE ON OVULATION IN FEMALE RATS TREATED WITH THE OESTROGEN ANTAGONIST ICI 46,474

1973 ◽  
Vol 72 (2) ◽  
pp. 345-350 ◽  
Author(s):  
P. G. McDonald

ABSTRACT A single dose (0.2 mg) of the antioestrogen ICI 46,474 at 15:00 h on the second day of dioestrus inhibited ovulation in the female rat. This inhibition could not be overcome by electrochemical stimulation of the basal hypothalamus on the afternoon of pro-oestrus. In contrast, progesterone (1.0 mg) treatment at 10:30 h on pro-oestrus induced ovulation at the expected time. The facilitatory effect of progesterone was prevented by administration of Nembutal (35 mg/kg) at 11:00 h on pro-oestrus. Progesterone did not induce ovulation in rats treated with ICI 46,474 on both dioestrus day 1 and 2. Sexual receptivity in ovariectomized oestradiol-treated (2.0 μg/day) rats was significantly depressed by the antioestrogen (1.0 mg/day) whether it was given 1 h before, 1 h after, or at the same time as the oestradiol. The compound also prevented the uterine weight increase in response to oestradiol but exerted a significant effect on uterine weight itself when compared to oil treated controls.

1976 ◽  
Vol 70 (3) ◽  
pp. 501-511 ◽  
Author(s):  
NANCY M. SHERWOOD ◽  
SHARON A. CHIAPPA ◽  
G. FINK

SUMMARY The effects of sex steroid hormones on the responsiveness of the neural mechanism responsible for the secretion of LH-RF have been examined in the female rat. Responsiveness was determined at pro-oestrus by measuring the increments in immunoreactive LH-RF of pituitary stalk blood produced by electrical stimulation of the medial preoptic area or median eminence. Ovariectomy on the morning of dioestrus reduced the LH-RF response to preoptic stimulation while oestradiol benzoate (OB) or testosterone propionate (TP) administered immediately after ovariectomy significantly augmented the response. The facilitatory effect of TP was possibly due to its conversion to an aromatized derivative since 5α-dihydrotestosterone monobenzoate was ineffective. Progesterone did not facilitate preoptic responsiveness, and, when administered to animals ovariectomized at 12.00 h of pro-oestrus, reduced the LH-RF response at 18.00 h the same day. Stimulation of the median eminence produced a significantly greater increment in LH-RF than stimulation of the preoptic area. The facilitatory action of OB on the LH-RF response was less marked for median eminence compared with preoptic stimulation. The administration of ICI 46474 at 17.00 h of dioestrus did not reduce preoptic responsiveness on the morning of the next day, suggesting that this compound does not act as an 'antioestrogen' at the level of the preoptic area.


1962 ◽  
Vol 39 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Roger A. Gorski ◽  
Charles A. Barraclough

ABSTRACT We have previously suggested that the failure of the androgen-sterilized, persistent-oestrous rat to ovulate, following electrical stimulation of the median eminence structures of the hypothalamus, is due to an insufficiency in adenohypophyseal LH concentration. Using the ovarian ascorbic acid technique for quantitative determination of pituitary LH content, the present studies have demonstrated that the sterile rat pituitary gland contains one-third the LH content of the normal prooestrous gland. Furthermore, not only does progesterone priming of this persistent-oestrous rat result in a 75 % increase in LH concentration, but on hypothalamic stimulation sufficient LH is released to induce ovulation. The decrease in LH concentration which accompanies ovulation in the progesterone-primed, sterile rat is approximately 45 % of the total gland content as compared with a 51 % decrease in pituitary content in the normal cyclic rat.


1965 ◽  
Vol 33 (3) ◽  
pp. 447-454
Author(s):  
M. J. K. HARPER

SUMMARY Administration of chlormadinone, an orally active progestational agent without significant oestrogenic activity, to intact immature female rats did not affect either ovarian or uterine weight significantly compared with controls. A single injection of human chorionic gonadotrophin (HCG) caused a 73 % increase in uterine weight in 24 hr. over the control value. This dose significantly increased ovarian weight and although it caused some stimulation of follicular development, ovulation during this time did not occur. When animals were treated with chlormadinone for 8 days, and received HCG on the 8th day, uterine weight was 170% greater than in the controls and 56% greater than with HCG alone. The uterine weight produced was similar to that found in animals treated with mestranol, a potent oestrogen, and HCG. In ovariectomized animals HCG did not affect uterine weight, while the small increase produced by chlormadinone was unaltered when HCG also was given. Mechanisms are discussed by which this augmentation of the uterine response to HCG might be produced. It seems most likely that chlormadinone administration causes storage of endogenous gonadotrophin in the pituitary, and that the exogenous gonadotrophin acts as the 'trigger' for the release of stored hormone, probably by a direct action on the hypothalamus.


1975 ◽  
Vol 67 (3) ◽  
pp. 419-424 ◽  
Author(s):  
CYNTHIA DOUGHTY ◽  
JANET E. BOOTH ◽  
P. G. McDONALD ◽  
R. F. PARROTT

SUMMARY Groups of neonatal female rats were treated for the first 5 days of life with oestradiol-17β, oestradiol benzoate or a synthetic oestrogen, 11β-methoxy-17-ethynyl-1,3,5(10)-oestratriene-3,17β-diol (RU 2858), in daily doses ranging from 0·5 to 1000 ng. Oestradiol-17β had no effect on adult ovarian cyclicity or sexual receptivity after ovariectomy and oestrogen + progesterone treatment. Ovarian cyclicity was prevented by 100 ng or more oestradiol benzoate/day, and by all doses of RU 2858. Only rats receiving 50 ng oestradiol benzoate/ day or 0·5 ng RU 2858/day showed normal receptivity. The defeminizing action of RU 2858 was at least 100 times greater than that of oestradiol benzoate; it is suggested that this greater potency is due to the low affinity of RU 2858 for the oestradiol-binding protein in the plasma of neonatal rats. These results indicate that defeminization of the neonatal rat brain can be induced by physiological amounts of oestrogen, and are discussed with reference to the action of testosterone.


1984 ◽  
Vol 103 (3) ◽  
pp. 317-325
Author(s):  
A. K. Brar ◽  
G. Fink

ABSTRACT The effects of catechol oestradiol and catechol oestrone on the release of LH and prolactin were investigated in immature male and female Wistar rats. In male rats both catechol oestradiol and catechol oestrone significantly increased the plasma concentration of LH, and catechol oestradiol but not catechol oestrone significantly increased the plasma concentration of prolactin and decreased the pituitary concentration of LH. The parent oestrogens, oestradiol-17β and oestrone, had no effect on plasma LH concentrations, but both increased significantly the plasma concentration of prolactin, and oestrone but not oestradiol-17β increased the pituitary concentration of LH. In immature female rats, catechol oestradiol inhibited the surge of LH and the increase in uterine weight induced by injecting pregnant mare serum gonadotrophin (PMSG). The injection of oestrone induced an increase in the plasma concentration of LH which was about nine times greater than that produced by oestradiol-17β. There were no significant differences in the effects of these steroids on plasma prolactin concentration. These results (i) confirm that in the immature male rat catechol oestrogens can stimulate LH release and show that catechol oestradiol can increase prolactin release, (ii) show that catechol oestradiol can inhibit the stimulatory effects of PMSG on LH release and uterine weight in the immature female rat, and (iii) demonstrate that oestrone can stimulate LH release in the immature female rat. J. Endocr. (1984) 103, 317-325


1970 ◽  
Vol 63 (3) ◽  
pp. 454-475 ◽  
Author(s):  
P. Petrusz ◽  
C. Robyn ◽  
E. Diczfalusy

ABSTRACT The biological effects of human follicle stimulating hormone (FSH) preparations were studied in intact immature female mice and in hypophysectomized immature female and male rats, following the complete neutralization of the luteinizing hormone (LH) content of human urinary menopausal gonadotrophin (HMG) preparations having – prior to neutralization – FSH:LH ratios ranging between 1.0 and 500.0. Neutralization of LH was achieved by the addition of rabbit anti-human chorionic gonadotrophin (HCG) sera of known anti-LH potency. The amount of anti-LH employed was 1.5 to 730 times more than that required for 100% neutralization. In intact immature female mice, such »LH-free« FSH preparations induced an increased ovarian weight, follicle stimulation, as well as a uterine weight increase. In immature hypophysectomized female rats, »LH-free« FSH preparations induced ovarian weight increase, growth and maturation of the Graafian follicles without repair of the deficient interstitial cells and without any signs of luteinization. These ovarian changes were associated with an increase in uterine weight and with vaginal cornification. In view of these data, it is concluded that human urinary FSH per se is capable of inducing oestrogen synthesis in hypophysectomized female rats. In immature hypophysectomized male rats, »LH-free« FSH preparations induced testicular enlargement without any stimulation of the testicular interstitial cells and without any growth of the ventral prostate and seminal vesicles. The same effects were obtained following a prolonged administration (3 weeks); spermiogenesis was stimulated, but no mature spermatozoa were found.


1978 ◽  
Vol 78 (1) ◽  
pp. 151-152 ◽  
Author(s):  
R. G. DYER ◽  
M. B. TER HAAR ◽  
LINDA C. MAYES

A.R.C. Institute of Animal Physiology, Babraham, Cambridge, CB2 4AT (Received 17 January 1978) For over 30 years, the method by which the brain regulates the secretion of gonadotrophic hormones has been studied by electrical stimulation of those parts of the central nervous system thought to be implicated in the control process. Much of the work has been performed on the female rat. In this species, anaesthetic doses of sodium pentobarbitone, administered immediately before the pro-oestrous 'critical period', block the preovulatory surge of luteinizing hormone (LH) for 24 h. The same treatment also reduces the early phase of the pro-oestrous secretion of follicle-stimulating hormone (FSH; Daane & Parlow, 1971). Electrical stimulation of the preoptic part of the hypothalamus can overcome this blocking effect and analysis of the optimum parameters required to restore normal secretion of gonadotrophins may give some insight into the endogenous process (e.g. Everett, 1965; Fink & Aiyer, 1974;


1958 ◽  
Vol 195 (1) ◽  
pp. 171-174 ◽  
Author(s):  
Vaughn Critchlow

In the present study, employing 38 female rats with normal estrous cycles, electrical stimulation during pentobarbital anesthesia was effective in inducing ovulation. It was found that bilateral stimulation of the hypothalamus in anesthetized proestrous rats during the ‘critical period’ and within certain spatial and current limitations consistently caused ovulation. The area that appears most responsive is medially situated in the ventral hypothalamus, between the optic chiasma and the infundibular stalk.


1971 ◽  
Vol 49 (3) ◽  
pp. 421-429 ◽  
Author(s):  
P. G. McDONALD ◽  
D. P. GILMORE

SUMMARY Electrochemical stimulation of the basal and preoptic hypothalamus, under sodium pentobarbitone anaesthesia, was carried out on the day of pro-oestrus in normal cycling and in ovarian hormone-treated female rats. Control rats ovulated in response to 25, 50 and 100 μA for 60 s in the median eminence and to 10 μA for 60 s in the preoptic area. Oestradiol (1 μg) given 24 h before median eminence stimulation significantly increased the number of rats ovulating. An injection of progesterone (1 mg) 24 h before median eminence stimulation did not affect the number of animals ovulating or the number of ova shed. In contrast, there was a significant reduction in the number of animals ovulating after preoptic stimulation. Stimulation of the median eminence 2–4 h after progesterone administration increased the number of animals ovulating. The results suggest that both oestradiol and progesterone exert a positive feedback effect at or below the level of the median eminence and that the negative feedback effect of progesterone is exerted on the preoptic area.


2001 ◽  
pp. 659-665 ◽  
Author(s):  
SN De Biasi ◽  
LI Apfelbaum ◽  
ME Apfelbaum

OBJECTIVE: The purpose of this work was to study the direct effect of leptin on LH release by anterior pituitary glands from female rats at the time of spontaneous and steroid-induced LH surge. METHODS: LH responsiveness to leptin by pituitaries from rats killed in the afternoon (1500 h) at different stages of the 4-day estrous cycle (diestrus-1: D1; diestrus-2: D2; proestrus; estrus), ovariectomized (OVX; 15 days post-castration) and ovariectomized steroid-primed (OVX-E(2)/Pg; pretreated with 5 microg estradiol and 1 mg progesterone), was evaluated in vitro. Hemi-adenohypophyses were incubated in the presence of synthetic murine leptin for 3 h. RESULTS: Addition of increasing concentrations of leptin (0.1-100 nmol/l) to the incubation medium of proestrus pituitaries produced a dose-related stimulation of LH release; the maximal increase to 315% of control was obtained with 10 nmol/l leptin. Leptin (10 nmol/l) enhanced LH release at all days of the estrous cycle, the greatest response occurring in proestrus (318%) and the lowest at D1 (123%). In order to evaluate the role of nitric oxide (NO) in the action of leptin on LH release, glands from proestrus rats were incubated in the presence of 10 nmol/l leptin with or without 0.3 mmol/l N(G)-monomethyl-l-arginine (NMMA), a competitive inhibitor of NO synthase (NOS). NMMA completely suppressed the stimulation of LH release induced by leptin. Leptin also stimulated LH release by pituitaries from OVX rats, and treatment with steroid hormones led to a marked increase in the response (OVX: 162% compared with OVX-E(2)/Pg: 263%; P<0.05). For comparative analysis, a similar experimental procedure was carried out using GnRH (10 nmol/l). Leptin acts at the pituitary level in a similar manner as GnRH, although with significantly lower potency. CONCLUSIONS: These results confirm and extend previous reports regarding a direct action of leptin at the pituitary level, stimulating LH release by anterior pituitaries from female rats at the time of spontaneous and steroid-induced LH surge. In the female rat pituitary this leptin action is controlled by gonadal steroids and mediated by NO.


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