IN-VITRO STUDIES OF THE EFFECTS OF OESTROGEN PRETREATMENT ON THE SENSITIVITY OF THE IMMATURE FEMALE RAT PITUITARY GLAND TO STIMULATION WITH GONADOTROPHIN RELEASING HORMONE

1977 ◽  
Vol 74 (1) ◽  
pp. 11-21 ◽  
Author(s):  
M. WILKINSON ◽  
D. DE ZIEGLER ◽  
DANIELLE CASSARD ◽  
K. B. RUF

The effects of oestrogen priming on the sensitivity of the anterior pituitary gland to stimulation with gonadotrophin releasing hormone (GnRH) was investigated in immature female rats using a new organ culture technique. Hemipituitary glands obtained from animals primed with a single dose of oestradiol benzoate (OB; 20 μg/100 g body weight) released significantly more LH when pulsed with GnRH (4 nmol/l) than did control hemipituitary glands. This potentiating effect was detectable as early as 5 days after birth. After a second stimulation, LH secretion remained high. These results were compared with those obtained from animals treated to induce increased levels of endogenous oestrogen on day 26 of life. Thus, hemipituitary glands were obtained from animals given two injections of OB, an injection of pregnant mare serum gonadotrophin (PMSG) or a unilateral brain lesion placed in the basal hypothalamus. Pituitary tissue was stimulated as before with a pulse of GnRH. Two injections of OB enhanced the sensitivity to stimulation. Conversely, both PMSG and lesion treatment severely reduced the sensitivity to GnRH, although PMSG-treated and lesioned animals have been used as models for the study of ovulation.

1977 ◽  
Vol 74 (1) ◽  
pp. 99-109 ◽  
Author(s):  
D. DE ZIEGLER ◽  
M. WILKINSON ◽  
DANIELLE CASSARD ◽  
K. B. RUF

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.


1982 ◽  
Vol 95 (1) ◽  
pp. 37-41 ◽  
Author(s):  
M. Wilkinson ◽  
R. Bhanot ◽  
J. A. Pincock ◽  
L. Donald

We have investigated whether sexual maturation in female rats is affected by repeated flurothyl-induced convulsions. This treatment had no effect on the normal age-related increase in body weight though puberty (vaginal opening) was significantly delayed when compared with non-convulsed control rats. In an attempt to probe the mechanism of this delaying effect we observed that (1) anterior pituitary response to gonadotrophin releasing hormone in vitro was normal in terms of LH release but FSH secretion was impaired and (2) progesterone injection in oestrogen-primed convulsed rats failed to generate an ovulatory-type surge of LH or FSH. Basal serum levels and basal in-vitro secretion of LH and FSH were normal. We conclude that repeated convulsions adversely affect the hypothalamo-pituitary-gonadotrophin system of immature female rats.


1977 ◽  
Vol 86 (4) ◽  
pp. 728-732 ◽  
Author(s):  
Y. Epstein ◽  
B. Lunenfeld ◽  
Z. Kraiem

ABSTRACT The aim of this study was to investigate effects of androgens on gonadotrophin release in response to gonadotrophin-releasing hormone (Gn-RH) stimulation in vitro. Hemipituitaries of mature male rats were pre-incubated for 90 min with T, DHT, 3α- or 3β-diol (4 ng or 4 μg/ml medium), and the incubation continued for 240 min after adding Gn-RH (1 ng/ml medium). Gn-RH caused a 4-5-fold rise in the secretion of LH and a 2-fold rise in FSH secretion. The effect of the androgens was dose-dependent. At low levels, T and DHT exerted no effect on Gn-RH-stimulated gonadotrophin release, whereas the two androstanediols (3α- and 3β-diol) augmented the Gn-RH stimulation of both gonadotrophins, though preferentially LH. With high doses of androgens, the results obtained showed: a) no effect of T; b) DHT suppression of the Gn-RH-stimulated FSH release; c) suppression of Gn-RH stimulation by 3α- and 3β-diol regarding both LH and FSH. It is concluded that T exerts through its reduced metabolites a feedback effect on the pituitary gland responsiveness to Gn-RH stimulation.


1992 ◽  
Vol 132 (3) ◽  
pp. 395-NP ◽  
Author(s):  
F. Kotsuji ◽  
K. Hosokawa ◽  
T. Tominaga

ABSTRACT Gonadotrophin-releasing hormone (GnRH) has been shown to regulate the synthesis and release of gonadotrophins acutely, yet few studies have investigated the chronic effects of this agent on pituitary gonadotrophins. In the present study we determined the effect of chronic administration of GnRH on the female rat pituitary gland. Rats of 8 weeks of age were injected s.c. with various doses of GnRH daily for 30 days. After completion of the GnRH treatment, treated rats and age-matched controls were killed by decapitation at 09.00 h on the first day of dioestrus, as determined from vaginal smears. Treatment with 10 ng–10 μg GnRH/day increased pituitary contents of FSH and LH in a dose-dependent manner. The change in FSH content was much greater than that of LH content. The pituitary FSH content of rats treated with 40 μg GnRH was significantly less than that of rats treated with 10 μg GnRH. There was a marked increase in the number of cells which stained positively for FSH (266%) and LH (28%) in the anterior pituitary of rats given 10 μg GnRH, but there was no demonstrable change in the areas of single cells stained positively for FSH and LH. Serum levels of LH, FSH and oestradiol were not affected by the GnRH treatment. These data indicate that chronic administration of GnRH is capable of increasing the pituitary gonadotrophin content and numbers of FSH and/or LH-stained cells and that FSH cells are affected more than LH cells by the GnRH treatment. The increase in pituitary gonadotrophin content, however, does not necessarily produce an increase in circulating levels of gonadotrophins. Journal of Endocrinology (1992) 132, 395–400


1985 ◽  
Vol 107 (1) ◽  
pp. 9-13 ◽  
Author(s):  
S. E. Inkster ◽  
R. N. Clayton ◽  
S. A. Whitehead

ABSTRACT The effects of neonatal monosodium l-glutamate (MSG) treatment on pituitary responsiveness to LH-releasing hormone (LHRH) and on pituitary LHRH receptors have been investigated in the intact adult female rat. Three- to four-month-old rats treated with MSG (4 mg/g body wt) on days 2, 4, 6, 8 and 10 after birth had significantly reduced ovarian and pituitary weights, showed an absence or disruption of ovarian cyclicity after puberty, and had significantly higher concentrations of serum prolactin despite normal levels of LH. In-vitro pituitary LH responses to LHRH were in the normal range for one group of treated animals whilst in a second group the LH responses were markedly enhanced. In contrast, the total number of pituitary LHRH receptors were significantly reduced in all MSG-treated animals showing that the increased pituitary responsiveness of MSG-treated animals is not attributable to an increase in pituitary LHRH receptors. J. Endocr. (1985) 107, 9–13


1981 ◽  
Vol 88 (3) ◽  
pp. 375-379
Author(s):  
J. DULLAART

Hemipituitary glands of immature female rats, aged 10, 15, 20, 25, 30 and 35 days and either ovariectomized or sham-operated 5 days earlier, were incubated for 2 h in vitro with or without LH releasing hormone. Concentrations of LH and FSH were determined at the end of the incubations in the incubation media and in the hemipituitary glands, and also in the sera collected at the beginning of the incubation experiments. Results showed that in many instances gonadotrophin release was higher after incubation of glands of ovariectomized rats than with glands of control animals. However, these effects of ovariectomy were much smaller than those observed in vivo and were generally absent in rats of less than 20 days of age. It was concluded that ovariectomy may change the secretory characteristics of the gonadotrophic cells of immature rats but that such changes were largely restricted to immature rats older than 20 days.


1993 ◽  
Vol 138 (2) ◽  
pp. 191-201
Author(s):  
D. W. Koppenaal ◽  
J. A. M. J. van Dieten ◽  
A. M. I. Tijssen ◽  
J. de Koning

ABSTRACT This study was designed to explore the efficacy of gonadotrophin-releasing hormone (GnRH) to antagonize the effect of gonadotrophin surgeinhibiting factor (GnSIF) on the timing of the induction by GnRH of the maximal self-priming effect on pituitary LH responsiveness. The GnSIF levels were increased by FSH treatment and reduced after gonadectomy. Female rats were injected s.c. with 10 IU FSH or saline (control) on three occasions during the 4-day cycle. Serial i.v. injections of GnRH (500 pmol/kg body weight) were administered to intact rats on the afternoon of pro-oestrus or 15–30 min after ovariectomy. Intact male rats were given 10 IU FSH and 500 or 2000 pmol GnRH/kg body weight on an equivalent time-schedule. Endogenous GnRH release was suppressed with phenobarbital. In intact female control rats, the timing of the maximally primed LH response was delayed as the GnRH pulse-interval increased. FSH treatment of female rats induced a suppression of the initial unprimed LH response and delayed the maximally primed LH response, which showed further delay as the GnRH pulse-interval was increased. When the pulsatile administration of GnRH was started 15–30 min after ovariectomy, the priming effect of GnRH did not change as the GnRH pulse-interval was increased in the saline-treated rats. However, FSH treatment caused a suppression of the unprimed LH response, a delay in the primed LH response and decreased the delay of the maximally primed LH response to GnRH when the GnRH pulse-interval was decreased. Increasing the interval between ovariectomy and the first GnRH pulse to 4 h diminished the efficacy of the FSH treatment: GnRH-induced priming was delayed by only one pulse instead of the two pulses in control rats. In intact males but not in orchidectomized rats, a self-priming effect was demonstrated during GnRH pulses which were 1 h apart. The effect of 2 nmol GnRH/kg body weight was the most pronounced. Compared with intact female rats, the timing of the maximally primed LH response was delayed by 1 h. FSH treatment did not affect the pituitary LH response to both dose levels of GnRH. It is concluded that FSH treatment increased the release of GnSIF by the ovary, then induced a state of low responsiveness of the pituitary gland to GnRH and subsequently delayed GnRH-induced maximal self-priming. The efficacy of GnRH to prime the pituitary gland was higher when GnSIF levels were decreasing after removal of the ovaries. On the other hand, GnSIF was more effective when the GnRH pulse-interval was increasing. This allows GnSIF more time to restore the unprimed state of the pituitary gland after each GnRH pulse-induced self-priming effect. It remains a matter of debate whether a similar mechanism of action is present in the male rat or whether this mechanism is suppressed by endogenous hormones such as androgens. Journal of Endocrinology (1993) 138, 191–201


1991 ◽  
Vol 130 (2) ◽  
pp. 169-175 ◽  
Author(s):  
T. Battmann ◽  
S. Mélik Parsadaniantz ◽  
B. Jeanjean ◽  
B. Kerdelhué

ABSTRACT The effects of substance P (SP) on the preovulatory surge of LH and on the inhibitory and stimulatory effects of oestradiol-17β and progesterone on gonadotrophin-releasing hormone (GnRH)-induced LH release were investigated in vivo and in vitro in the rat. A single s.c. injection of 100 μg SP at 12.00 h on the day of pro-oestrus significantly decreased the preovulatory surge of LH. In vitro, the inhibitory effect of oestradiol-17β on GnRH-induced LH release was not modified by treatment with SP. The stimulatory effect of progesterone on GnRH-induced LH release was reduced by treatment with SP. It is concluded that SP may play a modulatory role in the neuroendocrine control of the preovulatory LH surge. Journal of Endocrinology (1991) 130, 169–175


2000 ◽  
pp. 387-392 ◽  
Author(s):  
B Ishizuka ◽  
S Fusama ◽  
K Hirai ◽  
T Hosaka ◽  
N Hamada ◽  
...  

The objective of the study was to evaluate the effect of pretreatments such as gonadectomy in male and female rats, and gonadotropin-releasing hormone agonist (GnRHa) administration in female rats, on levels of secretion of melatonin, using an organ culture of pineal glands. Gonadectomy 2 weeks before the animal was killed increased the amount of melatonin secreted into the medium by the pineal glands of female rats but not of male rats. The increase in in vitro melatonin secretion after ovariectomy in female rats was prevented by estrogen replacement. Ovariectomy 3 and 4 weeks before death also significantly increased the amount of melatonin secretion. Administration of GnRHa 2 weeks before decapitation significantly decreased serum estradiol concentrations and significantly increased melatonin secretion by the pineal glands of female rat. GnRHa administration 3 or 4 weeks before decapitation also significantly decreased serum estradiol concentrations, but did not increase pineal secretion of melatonin. The results indicate that ovariectomy increases melatonin secretion from organ-cultured pineal glands and that this increase is suppressed by estrogen in adult female rats. In contrast, orchiectomy in male rats does not influence in vitro secretion of melatonin. These results suggest that the GnRH-gonadotropin system may participate in the regulation of pineal melatonin secretion in adult female rats.


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