Effect of oestrogen on the responsiveness of the pituitary gland to LRH: the role of corpora lutea

1981 ◽  
Vol 98 (1) ◽  
pp. 29-35
Author(s):  
T. R. Koiter ◽  
N. Pols-Valkhof ◽  
G. A. Schuiling

Abstract. The hypothesis that corpora lutea (CL) secrete substances which prevent oestrogens from influencing the state of responsiveness of the pituitary gland to LRH (RESP) was tested in rats rendered persistently oestrous (PO) by exposure to permanent illumination. In these rats ovulation and hence the presence of a single set of CL, was induced by exogenous gonadotrophin, hCG. The RESP of the animals was judged on 3 parameters based on the surge-like LH-secretory responses which were induced by 21-h long constant rate LRH infusions (104 ng/LRH/h). These 3 parameters were: a) the maximal height (MH) of the responses; b) the 'area under the curve' (AUC) of the LH values; and c) the constant β (or alternatively the t½) which characterizes the rate of decrease of the plasma LH concentrations after 2 h of infusion. Four experiments were performed, all with PO rats: 1) rats were injected with either oestradiol benzoate (OeB; 3 μg sc) or oil on day 0 (the day treatments were started was always denoted as day 0); 2) rats were treated similarly, but they also received an ovulatory dose of hCG (50 IU/100 g b.w. ip) on day 0; 3) rats were injected with hCG on day 0 and with OeB or oil on day 3; and 4) rats were injected with hCG on days 0 and 4, on which latter day they also received OeB or oil. In all 4 experiments the LRH infusions were started 21 h after administration of OeB or oil. Blood samples for LH determinations were taken at times apparent from 'Results and Discussion'. It is observed that: 1) after administration of OeB the MH and thereby the AUC increased significantly but the β of the LH-secretory responses was unchanged; 2) after administration of an ovulatory dose of hCG the LH-secretory responses changed also; of these responses, however, the β had decreased and the AUC had increased, whilst the MH remained unchanged; 3) when given together, OeB and hCG exhibited their effect simultaneously: the two effects are additive; 4) in the presence of 3-day old CL OeB is ineffective; and 5) in the presence of 4-day old CL neither OeB nor hCG is able to affect the RESP. It is concluded: 1) OeB and 'hCG' probably influence a different substrate of the LH-release mechanism; and 2) that these results confirm the hypothesis that CL secrete substances which prevent oestrogen from affecting the RESP for at least 4 days. If this hypothesis is extended to the cyclic rat, CL, arisen after the previous ovulation, may still be of importance on the day of the next pro-oestrus by exerting a significant influence on the RESP.

1983 ◽  
Vol 102 (2) ◽  
pp. 196-204 ◽  
Author(s):  
G. A. Schuiling ◽  
N. Pols-Valkhof ◽  
T. R. Koiter

Abstract. The LH releasing activities of LRH and the LRH-analogue buserelin® (HOE 766; (D-Ser (But)6-LRH(1–9)nona peptide-ethylamide) were compared in intact and short- and long-term castrated male rats, pre-treated (either 1 or 3 days) with oestradiol benzoate (EB) or oil. LRH and buserelin were infused iv at the constant rate of 104 ng/h for 21 h. Blood samples were taken from an intracarotid cannula. LH responses were judged on the basis of the mean maximal height of the LH concentration (MH; ng LH/ml plasma) and a parameter of total LH release, i.e. the area under the curve of LH concentrations plotted against time ('area under the curve', AUC; expressed in 'area units'). The release efficiency of LRH and buserelin, E (see for a definition: Materials and Methods), which informs on the total quantity of LH released in relation to pituitary LH content, was calculated by dividing the AUC × 100 by the pituitary LH content at the beginning of stimulation. Maximal plasma LH concentrations were observed between t= 1.5 and t=3 h after LRH and between t= 1.5 and t=9 after buserelin treatment. Both with LRH and buserelin the rise of LH secretion was greater the longer the animals were castrated and/or pre-treated with EB. The buserelin-induced LH response (with the exception of the responses induced in the EB-pre-treated, 4-weeks castrated rat) were about 2–2.5 times higher (MH) and larger (AUC) than the corresponding LRH-induced responses. The buserelin/LRH potency ratio, therefore, is about 2–2.5. EB-pre-treatment did not change the pituitary LH content. It therefore enhanced the efficiency of release of LH of both LRH and buserelin. Castration, on the other hand, caused an increase of the pituitary LH content: after 4 weeks it was raised by a factor 4. Since, however, the LH responses induced by LRH and buserelin were proportionally higher and larger, castration did not significantly change the efficiency of LH release. The results indicate that the efficiency of LH release can be changed by changes in the endocrine environment in the experimental animals, whilst for the magnitude of LH responses the pituitary LH content is also important. It is therefore suggested that the responsiveness of the pituitary gland to LRH (and agonistic analogues) is determined by (1) the state of the LH secretion mechanism and (2) the pituitary LH content.


1982 ◽  
Vol 92 (3) ◽  
pp. 327-339 ◽  
Author(s):  
E. TERASAWA ◽  
J. NOONAN ◽  
W. E. BRIDSON

Although the anterior pituitary gland has been shown to be a site of oestrogen feedback in the non-human primate, the role of the hypothalamus as a site of ovarian steroid feedback in facilitating gonadotrophin release has not been ruled out. In the present study, LH release in response to 2·5 mg progesterone with oestradiol benzoate (OB; 10 μg or 30 μg) 30 h earlier was observed in the ovariectomized monkey. Then pentobarbitone sodium was administered to block the progesterone-induced LH response. Serum levels of LH, oestradiol (OE2) and progesterone were measured by radioimmunoassay. In the first series of experiments a group of nine rhesus monkeys received subcutaneous implants of a small silicone elastomer capsule containing OE2. Two weeks later, either OB and oil, or OB and progesterone were injected sequentially. Oestradiol benzoate (10 μg) followed by oil 30 h later failed to cause any clear LH release, while 30 μg OB followed by oil induced a single peak of LH release with a peak latency of 16·5 ± 1·9 (s.e.m.) h after oil, and a duration of 69·8 ± 10·2 h. Regardless of the dose of OB, however, progesterone induced an LH release with two peaks in all animals. The peak latency (7·3 ±0·9 h) and the duration (19·3 ±1·3 h) of the first response with 30 μg OB + progesterone were virtually identical to those with 10 μg OB + progesterone (7·0 ±0·7 h, 18·0 ± 1·4 h respectively), whilst both components of the first response with 30 μg OB + progesterone were significantly shorter than those with 30 μg OB + oil (P < 0·001 for both). The peak latency of the second response with 30 μg OB + progesterone (42·7+ 4·8 h) was similar to that with 10 μg OB + progesterone (38·3 ±3·2 h), but the duration of the second response with 30 μg OB + progesterone (46·0 ± 1·7 h) was longer than that (35·7 ±3·2 h) with 10 μg OB + progesterone (P <0·02). In the second series of experiments the same nine animals received an OE2-capsule implantation and 10 μg OB (subthreshold) injections before pentobarbitone and progesterone. Pentobarbitone was first given 6 h before progesterone and additional injections were made to maintain the anaesthetized state for 21·6 ± 1·3 h. This period was to cover the progesterone-induced first LH response. Pentobarbitone completely blocked the expected first response of the progesterone-induced LH release in six animals. In the remaining three animals an enhanced LH surge occurred, but it consisted of a single peak with long latency 16·0 ± 2·0 h) and duration (66·0 ± 10·5 h) and was essentially the same as that observed in animals treated with a suprathreshold dose (30 μg) of OB alone. Anaesthesia did not, on the other hand, alter the response of the pituitary gland to LH releasing hormone. Therefore it was concluded that (1) sequential administration of oestrogen and progesterone induces an LH release with two phases in the ovariectomized monkey and (2) the facilitatory action of progesterone on the first phase of LH release requires the involvement of the brain.


1993 ◽  
Vol 139 (2) ◽  
pp. 253-258 ◽  
Author(s):  
A. M. Salicioni ◽  
R. W. Carón ◽  
R. P. Deis

ABSTRACT There is evidence that the adrenals play a role in the regulation of the synthesis and release of gonadotrophins in various vertebrates. The aim of this study was to determine the part played by adrenal steroids, with special reference to progesterone, on the concentration of LH in ovariectomized (OVX) and oestrogen-primed rats. OVX rats received a single s.c. injection of vehicle or oestradiol benzoate (OB, 20 μg/rat). This day was designated as day 0. Three or four days later (day 3–day 4), the rats were treated with mifepristone (10 mg/kg) or with two doses of progesterone antiserum and blood samples were obtained at 13.00 and 18.00 h. OB treatment of OVX rats reduced serum LH at 13.00 h and 18.00 h on day 3 but only at 13.00 h on day 4. The administration of mifepristone at 08.00 h to OVX and oestrogen-treated rats induced a significant increase in serum LH at 18.00 h on days 3 and 4, without modifying the values at 13.00 h. When mifepristone was given at 13.00 h a much larger increase in serum LH was obtained at 18.00 h. In OVX and oestrogen-treated rats, adrenalectomy on day 2 (08.00–09.00 h) induced an increase in serum LH at 18.00 h similar to that observed in the OVX and oestrogen-primed rats after mifepristone treatment. In order to determine the specificity of the effect of mifepristone, a group of OVX and oestrogentreated rats was injected with progesterone antiserum at 08.00 and 13.00 h on day 3. Serum LH concentrations at 13.00 and 18.00 h on day 3 were similar to values obtained in OVX rats treated with oestrogen and mifepristone. Serum progesterone was measured at 08.00 and 13.00 h in OVX and OVX and oestrogenprimed rats. At both times, values were similar in OVX rats but oestrogen treatment significantly increased serum progesterone levels. The important role of adrenal progesterone on the regulation of LH secretion in OVX and oestrogen-primed rats is evident from these results. Blocking progesterone action at the receptor level, we showed that OB significantly increased LH values at 18.00 h. On the basis of these studies it is tempting to speculate on the possibility of an inhibitory or stimulatory effect of oestrogen on serum LH concentration in OVX rats, according to the presence or absence of adrenal progesterone action. Journal of Endocrinology (1993) 139, 253–258


1974 ◽  
Vol 62 (3) ◽  
pp. 553-572 ◽  
Author(s):  
M. S. AIYER ◽  
G. FINK

SUMMARY The role of ovarian hormones in the development of increased sensitivity of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) which occurs before and during the preovulatory surge of luteinizing hormone (LH) in the rat has been examined. The response of the pituitary gland was determined, with respect to the secretion of LH and follicle-stimulating hormone (FSH), after the intravenous injection of 50 ng LH-RF/100 g body weight. The LH-RF was injected 30–60 min after the administration of sodium pentobarbitone at either 13.30 h or 18.80 h of pro-oestrus. Blood samples were collected immediately before and at frequent intervals after the injection of LH-RF, and the concentration of LH and FSH in these samples was measured by radioimmunoassay. Ovariectomy at 10.00–11.00 h of dioestrus reduced the LH response to LH-RF injected at 14.00 h of pro-oestrus, while oestradiol benzoate administered immediately after ovariectomy restored and even augmented this response. These data together with the finding that administration of the antioestrogen, ICI 46 474, at 17.00 h of dioestrus reduced the LH response to LH-RF injected on the afternoon of pro-oestrus indicates that the initial phase of increased pituitary sensitivity to LH-RF is dependent upon the marked rise in the concentration of oestradiol-17β in plasma which precedes the preovulatory surge of LH. The abrupt, marked increase in pituitary sensitivity to LH-RF, which, in the normal cycle, occurs between 14.00 and 18.30 h of pro-oestrus, failed to develop in rats ovariectomized on the morning of dioestrus whether or not oestradiol benzoate was administered after the operation. However, the LH response to LH-RF injected on the evening of pro-oestrus increased significantly when progesterone was administered at 13.00 h of pro-oestrus in rats ovariectomized and treated with oestradiol benzoate at 10.00–11.00 h of dioestrus. This suggests that the development of the second phase of increased pituitary sensitivity to LH-RF depends, at least partially, on progesterone acting on an oestrogen-primed pituitary gland. The concentrations of FSH in blood samples taken before injection of LH-RF at either 14.00 or 18.30 h of pro-oestrus were significantly greater in ovariectomized compared with those in sham-operated rats. In contrast the FSH responses, in terms of the mean maximal increments, were not significantly different in the various groups irrespective of the nature or time of operation or the time of injection of LH-RF. The FSH response to LH-RF was not appreciably altered by treatment with either oestradiol benzoate or progesterone immediately after ovariectomy although it was increased significantly by the sequential administration of oestrogen and progesterone. The significance of the findings that under certain conditions there were considerable differences between the LH and FSH responses to synthetic LH-RF is discussed with respect to the hypothesis that there is a common releasing factor for both gonadotrophins.


1981 ◽  
Vol 88 (2) ◽  
pp. 309-316 ◽  
Author(s):  
SUSAN C. WILSON ◽  
F. J. CUNNINGHAM

The role of oestradiol in the regulation of LH release in the hen was studied by use of the anti-oestrogen, tamoxifen (ICI 46,474). Intramuscular injection of laying hens with 2 or 4 mg tamoxifen on 2 successive days delayed or prevented the occurrence of the preovulatory release of LH and ovulation expected on day 3. Ovulation could be restored by i.v. injection of 20 pg LH releasing hormone (LH-RH). Tamoxifen at a dose of 1 mg affected neither the timing of the preovulatory release of LH nor ovulation. Treatment with 2 or 4 mg tamoxifen on 2 successive days reduced the effectiveness of an i.m. injection of progesterone to stimulate a release of LH. Injection of 1, 2 or 4 mg tamoxifen on 2 successive days significantly raised basal levels of LH in the blood at 24 h after the last injection. This was associated with an increase in the capacity of the pituitary gland to respond to an injection of synthetic LH-RH by a release of LH. These studies suggest that oestradiol has at least two roles in the regulation of LH release in the hen. First, it maintains a low basal level of LH in the blood by reducing the responsiveness of the pituitary gland to LH-RH. Secondly, oestradiol has a facilitative role in the mechanism by which progesterone stimulates the preovulatory release of LH.


1969 ◽  
Vol 60 (2) ◽  
pp. 184-198 ◽  
Author(s):  
Sidney J. Stolzenberg ◽  
Robert G. Eggert ◽  
Wayne H. Linkenheimer

ABSTRACT Female rats received pituitary autotransplants beneath the kidney capsule at 11 to 12 weeks of age or were hypophysectomized only at the metoestrous stage of the cycle. Subcutaneous injections of oestradiol benzoate (OB) were started 30 to 40 days following surgery in the first 3 experiments. In Experiments 1 and 2, Series 1 injections consisted of 50, 50 and 25 μg of OB given subcutaneously on days 0, 3 and 5. Series 2 injections were the same as Series 1 but given on days 16, 19 and 21. Pituitary grafts were removed from half of the rats on day 15 in Experiment 1. Ovarian weights were obtained on day 28. In Experiment 3, the dose of OB was raised to 100 μg per injection giving a total of 300 μg for each series. In Experiment 4, hypophysectomized rats without pituitary autotransplants were given Series 1 and 2 OB injections at the level of 125 μg per series. In Experiment 5, subcutaneous injections of OB were started 5 to 7 days following pituitary autotransplant. Rats were injected daily with 50 μg for 5, 10, 20, 40 and 80 days, with autopsies following 4 or 5 days after the last injection. In Experiment 6, 50 μg was injected daily in hypophysectomized rats without pituitary transplants for 5 and 20 days. The immediate effect of OB injections into rats bearing pituitary autografts was a significant (P < 0.01) increase in ovarian weight. Long term treatment (> 40 days) caused a significant (P < 0.05) decrease in ovarian weight. Short term treatment followed by a 23 or 35 day period of no treatment gave an even greater decrease in ovarian weight (P < 0.01). Hypophysectomized rats showed no effect on ovarian weights with similar OB treatments, indicating the importance of the pituitary gland in this response. Removal of the autotransplanted pituitary gland 10 days after the first series was completed, had no apparent effect on regression of the corpora lutea. There was no effect on adrenal weight in any of the experiments. It is suggested that oestrogens initiate a process which ultimately results in luteal regression in rats bearing pituitary autografts.


1980 ◽  
Vol 95 (2) ◽  
pp. 158-165 ◽  
Author(s):  
J. Roos ◽  
S. Plas-Roser ◽  
Cl. Aron

Abstract. The aim of this work was to determine whether changes in pituitary responsiveness to LRH could account for the effect of testosterone propionate (TP) on the gonadotrophic function of the pituitary in 4-day cyclic female rats. Doses of 250, 500 and 1000 ng LRH were injected ip on pro-oestrus at 15.30 h in rats either pre-treated with 5 mg TP on dioestrus II at 10.00 h or injected with 30 mg/kg pentobarbital (PB) at 13.00 h. LH release induced within 30 min by LRH was higher in PB than in TP-treated rats. Even by using 250 ng LRH full ovulation was observed on the morning of oestrus in PB-treated rats. On the other hand, only partial ovulation occurred whatever the dose of LRH used in TP-treated rats; a great number of luteinized follicles was shown to be constantly associated with post-ovulatory corpora lutea. While LRH caused a significant FSH release (30 min later) in TP-treated rats, no FSH release could be shown in PB-treated rats. The pituitary FSH content appeared to be decreased and the pituitary LH content remained unchanged while a sharp increase in both blood FSH and LH concentrations occurred following injection of 1000 ng LRH in TP-treated rats. Concomitantly a sharp decrease in the number of pituitary gonadotrophs (AB-PAS+) was observed. A significant decrease in the number of the small roundshaped PAS positive cells was also observed. The mechanisms whereby TP influences the function of the pituitary-ovarian axis are discussed in the light of these results.


1978 ◽  
Vol 78 (3) ◽  
pp. 451-452
Author(s):  
R. G. GOSDEN

Department of Physiology, University Medical School, Teviot Place, Edinburgh, EH8 9AG (Received 20 March 1978) Ageing female rats maintained under standard laboratory lighting conditions (14 h light: 10 h darkness) frequently enter a state of persistent vaginal cornification because the pituitary gland fails to provide an ovulatory surge of gonadotrophic hormones. The ovaries of such animals become dominated by growing and cystic follicles as the corpora lutea disappear. The concentrations of prolactin in the pituitary gland and the circulation during persistent oestrus are known to be raised for at least part of the day (Clemens & Meites, 1971; Mallampati & Johnson, 1974; Shaar, Euker, Riegle & Meites, 1975; J. E. Beach, R. G. Gosden & J. W. Everett, unpublished observations). A possible antigonadotrophic role of prolactin in the aetiology of the persistent oestrous condition should be considered because of the known inverse relationship between the release of prolactin and gonadotrophins


Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 812-820 ◽  
Author(s):  
Angela Chambery ◽  
Augusto Parente ◽  
Enza Topo ◽  
Jordi Garcia-Fernàndez ◽  
Salvatore D'Aniello

GnRH, originally isolated from mammalian hypothalamus, is a key player in the control of vertebrate reproduction. Employing reverse-phase chromatography, we purified a peptide of relative molecular mass of 1182.60 Da from the cephalochordate amphioxus Branchiostoma lanceolatum. We found that its amino acid sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) was identical to that of mammalian GnRH. The highest concentrations (4.04 ± 0.3 μg/g tissue), localized in the anterior part of the body, occurred in November, a time when amphioxus gonads prepare for the seasonal spawning. Furthermore, the biological activity of amphioxus GnRH was investigated by examining its capability to elicit LH release from the rodent pituitary gland. The origins of GnRH can be traced back to the origins of chordates. The seasonal variations of amphioxus GnRH also suggest an ancient role of this peptide in the control of reproduction in chordates, even before the evolution of a proper pituitary gland. Data show that the isolation of a GnRH hormone in the cephalochordate Amphioxus could have a pivotal role in reproduction.


1986 ◽  
Vol 110 (3) ◽  
pp. 499-505 ◽  
Author(s):  
N. J. MacLusky ◽  
L. C. Krey ◽  
B. Parsons ◽  
G. R. Merriam ◽  
D. L. Loriaux ◽  
...  

ABSTRACT The role of catechol oestrogen formation in the mechanism by which circulating oestrogens facilitate gonadotrophin release and female sexual behaviour was explored in adult female rats. The effects of oestradiol-17β were compared with those of a group of oestrogens with either a reduced affinity for oestrogen receptors (oestradiol-17α) or a reduced ability to act as substrates for catechol oestrogen formation (2-fluoro-oestradiol, 4-fluoro-oestradiol and moxestrol (11β-methoxy-17α-ethynyloestradiol)). Rats were ovariectomized on the evening of dioestrus day 1 of the 4-day oestrous cycle and implanted s.c. 12 h later with infusion pumps containing either one of the test oestrogens or vehicle alone. Infusion rates for oestradiol-17β, moxestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol were adjusted to give concentrations of nuclear oestrogen receptors in the brain and pituitary gland within the range of those found in intact female rats during pro-oestrus. Oestradiol-17α was infused at the same and at a tenfold higher rate than that of oestradiol-17β; neither of these treatments with oestradiol-17α significantly increased brain or pituitary gland nuclear oestrogen receptor levels. On the day after the pump was implanted, samples of tail vein blood were withdrawn at 12.00, 14.00, 16.00 and 18.00 h for LH assay. All animals were then injected s.c. with 1 mg progesterone in propylene glycol, and tested for feminine sexual behaviour 5 h later. Oestradiol-17β, moxestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol all elicited pronounced LH surges and facilitated progesterone-triggered proceptive and lordosis behaviours. In contrast, oestradiol-17α was without effect on LH secretion and sexual behaviours. These results are consistent with the hypothesis that catechol oestrogen biosynthesis is not an obligatory step in the mechanism by which circulating oestrogens induce LH release and feminine sexual behaviour in the rat. J. Endocr. (1986) 110, 499–505


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