Inhibition of phasic but not tonic pituitary secretion by 2-hydroxyoestrone in the rat: evidence of action as an oestrogen antagonist

1983 ◽  
Vol 98 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Shigehiro Katayama ◽  
Jack Fishman
Keyword(s):  
Pituitary Hormones ◽  
Ovariectomized Rats ◽  
Priming Dose ◽  
Physiological Mechanisms ◽  
Lh Surge ◽  
Oestradiol Benzoate ◽  
Pituitary Secretion ◽  
The Brain ◽  
Phasic Release

Rats with 4-day oestrous cycles, implanted with intracardiac catheters, were injected with 2-hydroxyoestrone at noon on pro-oestrus and their plasma LH levels monitored at frequent intervals thereafter. A dose of 100 μg 2-hydroxyoestrone completely abolished the preovulatory LH rise in four out of ten animals tested, showing no effect in the six others. When an injection of 10 μg oestradiol 1 h before the 2-hydroxyoestrone administration was given all the rats showed an absence of the preovulatory LH surge, while it remained intact in the controls treated with oestradiol only. The principal metabolite of 2-hydroxyoestrone, 2-methoxyoestrone, exhibited no influence on the pituitary gonadotrophin release. Repeated injections of 100 pg doses of 2-hydroxyoestrone to long-term ovariectomized rats produced no change in plasma LH and prolactin levels. In animals primed with oestradiol benzoate, 2-hydroxyoestrone given 1–2 h after the priming dose blocked the phasic release of the pituitary hormones on the afternoon of the 2 subsequent days. The LH and prolactin surges in the primed animals, however, were not affected when the catechol oestrogen was injected 2 h before their appearance. These results indicate that in the cyclic rat exogenous 2-hydroxyoestrone inhibits the preovulatory LH surge when its administration is coincident with the preovulatory oestradiol rise. In the ovariectomized rat 2-hydroxyoestrone inhibits the oestrogen-dependent priming step but does not affect either the oestrogen-independent expression of the induced surges or the tonic secretion of these pituitary hormones. These results indicate a dissociation of central and peripheral activities in this oestradiol metabolite and suggest that this catechol oestrogen functions as an oestrogen antagonist in neuroendocrine events. Since catechol oestrogens can be formed in the brain these pharmacological responses may reflect physiological mechanisms.

Antioestrogen inhibition of oestradiol-induced alterations in hypothalamic noradrenaline turnover

1985 ◽  
Vol 106 (1) ◽  
pp. 37-42 ◽  
Author(s):  
C. Hiemke ◽  
B. Poetz ◽  
R. Ghraf
Keyword(s):  
Brain Area ◽  
Serum Levels ◽  
Ovariectomized Rats ◽  
Noradrenaline Turnover ◽  
Stimulatory Action ◽  
Enhanced Sensitivity ◽  
Oestradiol Benzoate ◽  
Lh Release ◽  
Secretory System

ABSTRACT Long-term (4–6 weeks) ovariectomized rats were injected with either oestradiol benzoate (OB; 20 μg s.c.) or monohydroxytamoxifen (MTAM; 0·2 mg i.p.) plus OB. Oestradiol benzoate was administered at 12.00 h on day 0 and MTAM was given immediately before OB, followed by further injections twice daily to maintain sufficiently high antioestrogen levels. When given alone, OB reduced the serum levels of LH during the morning (08.00–09.00 h) and afternoon (17.30–18.30 h) hours of day 3 after priming. The feedback actions of OB on LH release were accompanied by time-dependent alterations of noradrenaline turnover in the preoptic–anterior hypothalamic brain area (POAH). On day 3 after priming the noradrenaline turnover rate was reduced in the morning and increased in the afternoon. The increase correlated with an enhanced sensitivity of the LH secretory system to progesterone. The antioestrogen MTAM blocked the OB-induced sensitization of LH release to the stimulatory action of progesterone and interfered with the stimulatory long-term effect of oestradiol on hypothalamic noradrenaline turnover. The data strongly support the view that the oestrogen-induced afternoon increase of noradrenaline turnover in the POAH represents a pre-requisite for the induction of LH surges. The stimulatory effect of oestradiol on hypothalamic noradrenaline turnover seems to be mediated by a classical oestrogen receptor mechanism. J. Endocr. (1985) 106, 37–42

RESTORATION BY OESTRADIOL BENZOATE OF A NEURAL AND HORMONAL RHYTHM IN THE OVARIECTOMIZED RAT

1975 ◽  
Vol 64 (1) ◽  
pp. 27-35 ◽  
Author(s):  
F. R. BURNET ◽  
P. C. B. MACKINNON
Keyword(s):  
Single Injection ◽  
Time Of Day ◽  
Ovariectomized Rats ◽  
Female Rat ◽  
Functional Link ◽  
Initial Injection ◽  
Oestradiol Benzoate ◽  
Before And After ◽  
Lh Release ◽  
The Brain

SUMMARY The rate of [35S]methionine incorporation into protein in discrete cerebral areas was measured before and after the administration of oestradiol benzoate (OB) to chronically ovariectomized rats. The circadian rhythm of incorporation which is normally seen in the intact cyclic female rat was deleted by ovariectomy. A daily rhythm of incorporation reappeared, however, in all the brain areas studied 30 h after a single injection of OB (20 μg), and was still present 12 days later. The release of luteinizing hormone (LH) after administration of 20 μg OB was measured in chronically ovariectomized animals and was found to be biphasic. High levels of LH after ovariectomy were initially reduced by negative feedback, but this phase was followed 52 h later by a facilitation of LH release between 15.00 and 18.00 h. The facilitation of LH release at this time of day was still detectable 12 days after the initial injection. The evidence for a functional link between the rhythm of neural activity which is reflected by [35S]methionine incorporation, and the ability to 'time' the facilitation of LH release is discussed.

Dissociation between the ovarian factors controlling sexual receptivity and preovulatory secretion of LH in cyclic female rats

1987 ◽  
Vol 112 (1) ◽  
pp. 133-138 ◽  
Author(s):  
P. Södersten ◽  
P. Eneroth
Keyword(s):  
Sexual Behaviour ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Sexual Receptivity ◽  
Serum Progesterone ◽  
Lh Surge ◽  
Oestradiol Benzoate ◽  
Lh Release ◽  
Lh Secretion ◽  
Intact Rats

ABSTRACT Ovariectomy and treatment with oestradiol benzoate (10 μg OB) on the day before behavioural oestrus eliminated the preovulatory surge of LH and reduced the level of sexual receptivity on the following day. Sexual behaviour, but not the LH surge, was restored by progesterone (0·5 mg) given 18 h later. Injection of OB on the day after behavioural oestrus induced a small release of LH and normal sexual behaviour on the following day. Ovariectomy on the day after behavioural oestrus reduced the stimulatory effect of OB on sexual behaviour and eliminated its weakly stimulatory effect on LH release. Sexual behaviour, but not the small LH surge, was restored in these animals by progesterone (0·5 mg) given 18 h later. Treatment of rats ovariectomized 2 days before the day of the LH surge with implants containing oestradiol or injections of oestradiol (1 μg) induced LH surges but the amplitudes of these LH surges were much smaller than those of the normal LH surge. Treatment of intact rats with OB increased serum progesterone levels 24 h later, an effect which was eliminated by ovariectomy. Injections of LH (20 μg) into intact rats on the day after behavioural oestrus also increased serum progesterone concentrations but failed to stimulate sexual behaviour. It is suggested that OB treatment of intact rats on the day after behavioural oestrus stimulates sexual behaviour by inducing a surge of LH secretion which activates ovarian secretion of progesterone. Thus, oestrogen and progesterone but not the LH surge are essential for sexual behaviour. Whereas oestradiol and progesterone restore normal sexual behaviour in ovariectomized rats, additional ovarian factors may be required for induction of normal LH surges. J. Endocr. (1987) 112, 133–138

Effects of oestradiol benzoate and progesterone on luteinizing hormone release and catecholamine turnover in the preoptic-hypothalamic brain area of ovariectomized rats

1983 ◽  
Vol 97 (3) ◽  
pp. 437-445 ◽  
Author(s):  
C. Hiemke ◽  
D. Frohne ◽  
D. Bruder ◽  
R. Ghraf
Keyword(s):  
Brain Area ◽  
Serum Levels ◽  
Ovariectomized Rats ◽  
Time Interval ◽  
Dopamine Turnover ◽  
Noradrenaline Turnover ◽  
Serum Lh ◽  
Short Term Exposure ◽  
Oestradiol Benzoate

At noon, long-term (4–6 weeks) ovariectomized rats were exposed for 6–78 h to a single subcutaneous injection of oestradiol benzoate (20 μg) which significantly reduced the serum levels of LH over the whole time-interval investigated. The negative feedback action of oestradiol was accompanied by reduced turnover of both noradrenaline and dopamine in the preoptic-anterior hypothalamic brain area (POAH), but not in the mediobasal hypothalamus, 6, 68 and 72 h after administration of the hormone. Between 72 and 78 h after oestradiol-priming an afternoon increase of noradrenaline turnover was observed in the POAH. In rats primed with oestradiol benzoate for 72 h, short-term exposure (6 h) to progesterone (2·5 mg) induced a marked surge of serum LH and FSH in the late afternoon. In the POAH of these rats progesterone did not interfere with the afternoon increase of noradrenaline turnover induced by oestradiol-priming. However, it markedly increased the dopamine turnover rate of primed rats, thus reversing the inhibitory action of oestradiol benzoate on the dopaminergic system of the POAH. It is concluded that both the noradrenergic and the dopaminergic neurones of the POAH are involved in the negative and positive feedback actions of oestradiol and progesterone on LH and FSH release. The paper discusses whether the oestradiol-induced afternoon increase in noradrenaline turnover represents a prerequisite for the induction of LH surges by progesterone.

A possible role of clomiphene citrate in the control of pre-ovulatory LH surge during induction of ovulation

1985 ◽  
Vol 109 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Naoki Terakawa ◽  
Ikuya Shimizu ◽  
Hirohisa Tsutsumi ◽  
Toshihiro Aono ◽  
Keishi Matsumoto
Keyword(s):  
Nuclear Receptor ◽  
Clomiphene Citrate ◽  
Ovariectomized Rats ◽  
Receptor Complex ◽  
Oestrogen Receptors ◽  
Lh Surge ◽  
Serum Lh ◽  
Lh Release

Abstract. A possible role of clomiphene citrate (clomiphene) in the control of ovulation in anovulatory women was investigated. Since a single ip administration of 5 μg oestradiol-17β (E2) to long-term ovariectomized rats did not induce LH surge, the following studies were designed to determine whether pretreatment with clomiphene followed by administration of E2 could induce LH surge in the ovariectomized rats. Changes in cytoplasmic and nuclear oestrogen receptors (ER) were also examined in the pituitaries of these animals. An ip injection of 200 μg clomiphene suppressed serum LH levels significantly for 72 h. The clomiphene injection rapidly caused an elevation of nuclear ER with a concomitant depletion of cytoplasmic ER level in the pituitary and the ER levels remained almost unchaged for 72 h. An administration of E2 12 or 24 h after the clomiphene injection had no significant effects on either the serum LH levels or the cytoplasmic and nuclear ER levels, compared with those induced by clomiphene alone. However, LH surge and the depletion of nuclear ER in the pituitary occurred 24 h later when E2 was injected 48 h after the clomiphene administration. The E2-induced LH release seems to be induced by a replacement of clomiphene by E2 on the nuclear receptor complex. These results suggest that clomiphene may exert actions directly on the pituitary gland to augment oestrogeninduced LH release.

SECRETION OF LUTEINIZING HORMONE CAUSED BY CONTINUOUS INFUSIONS OF LUTEINIZING HORMONE RELEASING HORMONE IN THE LONG-TERM OVARIECTOMIZED RAT: EFFECT OF OESTROGEN PRETREATMENT

1976 ◽  
Vol 71 (1) ◽  
pp. 1-11 ◽  
Author(s):  
G. A. SCHUILING ◽  
H. P. GNODDE
Keyword(s):  
Luteinizing Hormone ◽  
Pituitary Gland ◽  
Ovariectomized Rats ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Clear Cut ◽  
Oestradiol Benzoate ◽  
Maximal Plasma ◽  
Lh Rh

SUMMARY Continuous infusions of luteinizing hormone releasing hormone (LH-RH) into phenobarbitone-treated long-term ovariectomized rats, resulted in patterns of LH secretion which were determined by the blood LH-RH concentration. Infusions of 52 ng LH-RH/h caused steadily increasing plasma LH levels, which stabilized after about 2 h of infusion and were maintained for the rest of the experiment (9 h). A similar course of plasma LH concentration was observed as a result of infusions of 104 ng LH-RH/h, though in this case LH concentrations reached higher levels than those induced by infusion of 52 ng LH-RH/h. Higher rates of LH-RH infusion (208 and 416 ng/h), however, induced clear-cut LH peaks, which reached their maximal plasma values after 2–3 h of infusion and then declined again until, at the end of the experiment, they were only slightly higher than the LH levels induced by infusions of 52 ng LH-RH/h. A similar series of LH-RH infusions given to ovariectomized rats pretreated with oestradiol benzoate during 3 days (the rats were injected daily with 7 μg steroid), produced a highly augmented response of the pituitary gland, but all LH-RH concentrations infused induced rather sharp LH peaks, reaching their maximum after 2–3 h of infusion. After 5 h of infusion the descending parts of all these peaks appeared to converge. In both control and oestradiol benzoate-pretreated rats there appeared to be a linear relationship between the logarithm of the blood LH-RH concentration and the maximal plasma LH values on one hand, and the amount of LH secreted during the first 5 h of infusion on the other. Furthermore, it appeared that the longer the period of oestrogen action, the more the response of the pituitary gland to a certain dose of LH-RH was enhanced.

Naloxone reverses post-ejaculatory inhibition of sexual behaviour in female rats

1987 ◽  
Vol 113 (3) ◽  
pp. 429-434 ◽  
Author(s):  
G. Forsberg ◽  
I. Bednar ◽  
P. Eneroth ◽  
P. Södersten
Keyword(s):  
Sexual Behaviour ◽  
Opioid Peptide ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Sexual Receptivity ◽  
Peptide Receptor ◽  
Oestradiol Benzoate ◽  
Brain And Spinal Cord ◽  
The Brain

ABSTRACT Sexual receptivity was inhibited in ovariectomized rats treated with oestradiol benzoate (OB: two injections of 2 μg) and progesterone (0·5 mg) immediately after ejaculation by the male and restored after the end of the post-ejaculatory refractory period in the male. The post-ejaculatory inhibition of sexual receptivity was reversed by i.p. (5 mg), intracerebroventricular (50 μg) or intrathecal (50 μg) injection of the opioid peptide receptor antagonist naloxone. The concentration of serum β-endorphin-like immunoreactivity in ovariectomized rats treated with OB plus progesterone was unaltered by sexual interactions with males (18·3 ± 6·0 (s.e.m.), 26·4 ± 2·1 and 21·8 ± 6·1 pmol/l before sexual activity, after ejaculation and after the end of the post-ejaculatory interval) but reduced to non-detectable by hypophysectomy. Subcutaneous injection of 10 μg β-endorphin raised serum concentrations of β-endorphin-like immunoreactivity but did not affect the display of sexual behaviour. The behaviour was also unaffected by intracerebroventricular injection of 0·1, 0·2 or 1·0 μg β-endorphin or by injections of 0·25 μg β-endorphin in the periaqueductal central grey of the mesencephalon. The results show that ejaculation by male rats causes a transient inhibition of sexual receptivity in the female which may be dependent upon opioid peptide receptor mechanisms in the brain and spinal cord. It is unlikely that the peptide is β-endorphin. J. Endocr. (1987) 113, 429–434

LUTEINIZING HORMONE RELEASING FACTOR IN PITUITARY STALK PLASMA FROM LONG-TERM OVARIECTOMIZED RATS: EFFECTS OF STEROIDS

1980 ◽  
Vol 86 (3) ◽  
pp. 511-524 ◽  
Author(s):  
D. K. SARKAR ◽  
G. FINK
Keyword(s):  
Anterior Pituitary ◽  
Pituitary Stalk ◽  
Ovariectomized Rats ◽  
Circadian Pattern ◽  
Diurnal Pattern ◽  
Peripheral Plasma ◽  
Oestradiol Benzoate ◽  
Lh Release ◽  
Venous Plasma

The concentration of LH releasing factor (LH-RF) was measured by radioimmunoassay in blood collected from the cut pituitary stalk of long-term ovariectomized rats anaesthetized with Althesin. Stalk plasma LH-RF concentrations were increased immediately after ovariectomy (carried out at oestrus) and low at 2 and 4 days after operation. The concentrations then began to increase to reach a level at 24–28 days which was significantly higher than the concentrations during the oestrous cycle except for the time of the ovulatory surge at pro-oestrus. This pattern was similar to that of the concentrations of LH in jugular venous plasma taken from the same animals before exposure of the pituitary stalk. Like peripheral plasma LH concentrations, the concentrations of LH-RF in stalk plasma fluctuated and fell significantly and rapidly after the intravenous injection of 1 μg oestradiol-17β. The release of LH-RF in long-term ovariectomized rats, into which had been implanted an oestradiol-containing Silastic capsule, was similar to the diurnal pattern of LH release; the afternoon increase in stalk plasma LH-RF concentration could be blocked by sodium pentobarbitone administered at 13.00 h and augmented by administering this anaesthetic at 13.00 h of the preceding day. The stalk plasma LH-RF concentrations in animals injec[unk]d with oestradiol benzoate (OB) followed 72 h later with either OB or progesterone were lower than the concentrations in animals injected only with oil. These data show that in the rat (1) ovarian steroids could moderate LH release ('negative feedback') by inhibiting LH-RF release, and that in long-term ovariectomized animals (2) the oestradiol-induced circadian pattern of LH release is due to a circadian pattern of LH-RF release, and (3) the surge of LH produced by administering OB followed by either OB or progesterone is probably due mainly to a massive increase in the responsiveness of the anterior pituitary gland to LH-RF.

DYNAMIC CHANGES IN HYPOTHALAMIC LH-RH LEVELS ASSOCIATED WITH THE OVARIAN STEROID-INDUCED GONADOTROPHIN SURGE

1979 ◽  
Vol 92 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Satya P. Kalra ◽  
Pushpa S. Kalra
Keyword(s):  
Temporal Changes ◽  
Ovariectomized Rats ◽  
Ovarian Steroid ◽  
Dynamic Changes ◽  
Medial Basal Hypothalamus ◽  
Lh Surge ◽  
Serum Lh ◽  
Oestradiol Benzoate ◽  
Definite Pattern ◽  
Lh Rh

ABSTRACT Pro-oestrous-type LH surges were induced by treating ovariectomized rats (day 0) with either oestradiol benzoate (OeB, 40 μg/rat) or oestrogen (10 μg/rat followed by progesterone (4 mg/rat, day 2, OeBP). To characterize the temporal changes associated with the LH surge on day 2, LH-RH levels in the medial basal hypothalamus (MBH) and the pre-optic area (POA) were analyzed by RIA in rats sacrified at hourly intervals between 10.00–19.00 h. Following these treatments the LH-RH content of POA fluctuated somewhat but no definite pattern was observed. In OeB rats, the MBH LH-RH levels were unchanged through the initial LH surge period (13.00–15.00 h) declining significantly, as in the OeBP group, near the end of the surge period (19.00 h). However, in OeBP rats, the MBH LH-RH contents decreased at 14.00 h and these were followed by markedly elevated levels between 15.00–17.00 h coincident with maximal increments in serum LH. The OeBP group alone showed a surge of serum FSH.

Vasoactive intestinal peptide inhibits the steroid-induced LH surge in the ovariectomized rat

1992 ◽  
Vol 133 (3) ◽  
pp. 433-437 ◽  
Author(s):  
R. F. Weick ◽  
K. M. Stobie
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Critical Period ◽  
Control Sample ◽  
Ovariectomized Rats ◽  
Lh Surge ◽  
The Third ◽  
Oestradiol Benzoate ◽  
Short Time ◽  
Lh Secretion ◽  
Secretion Rates

ABSTRACT The LH surge was induced in ovariectomized rats by sequential treatment with oestradiol benzoate and progesterone. Vasoactive intestinal peptide (VIP) or saline was infused into the third cerebral ventricle from 13.30 to 16.30 h on the afternoon of the anticipated LH surge. Two blood samples were taken by jugular puncture from each animal, one at 12.00 h as a control sample and the other at 16.00, 18.00, 20.00 or 22.00 h. Saline-infused animals showed a normal LH surge, with mean plasma LH concentrations reaching a peak at 18.00 h, declining by 20.00 h and reaching control (12.00 h) levels by 22.00 h. Plasma LH in animals infused with VIP was not significantly higher than control levels at 16.00 or 18.00 h. By 20.00 h, mean LH levels in VIP-infused rats had risen to the levels seen at that time in saline-infused rats, and by 22.00 h LH had returned to control levels in VIP-infused animals. We interpret these findings to mean that VIP inhibits LH secretion during the LH surge. It does not block the surge completely, as pentobarbital during the critical period would have done; nor does VIP appear to affect the timing of the LH surge. Rather, VIP inhibits the increased LH secretion rates of the LH surge only during the period of VIP treatment and for a short time afterward. Journal of Endocrinology (1992) 133, 433–437

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