A POSSIBLE MECHANISM OF THE OVULATION-INHIBITING EFFECT OF CHLORMADINONE ACETATE IN THE RAT

1968 ◽  
Vol 41 (3) ◽  
pp. 353-362 ◽  
Author(s):  
F. DÖCKE ◽  
G. DÖRNER ◽  
K.-H. VOIGT
Keyword(s):  
Effective Dose ◽  
Median Eminence ◽  
Anterior Pituitary ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Main Site ◽  
Chlormadinone Acetate ◽  
Inhibiting Effect ◽  
Competitive Antagonism ◽  
Site Of Action

SUMMARY To study the mechanism of the ovulation-inhibiting effect of chlormadinone acetate, different quantities of this progestogen were implanted into one or both ovaries of dioestrous female rats. Introduction of the subcutaneously effective dose into one ovary suppressed ovulation in both, but implantation of half of this quantity did not influence spontaneous ovulation. On the other hand, 1/100 of the subcutaneously effective dose, implanted into the medio-basal hypothalamus or the anterior pituitary of adult dioestrous female rats, and of prepubertal females simultaneously injected with oestradiol benzoate, inhibited spontaneous and oestrogen-induced ovulations respectively. In juvenile rats the main site of action was the median eminence—anterior pituitary region. Chlormadinone was then implanted into the anterior hypothalamus or the anterior pituitary of adult dioestrous rats, and the median eminence was electrically stimulated during the 'critical period' in pro-oestrus. Since implants in the adenohypophysis prevented ovulation whereas implants in the anterior hypothalamus did not, a hypophysial site of action is suggested. On the basis of these results and of former findings on the action of oestrogens in ovulation, a hypothesis involving a competitive antagonism between oestrogen and progestogen at the hypophysial level is advanced to explain the acute ovulatory effects of these steroids.

THE MECHANISM OF THE INDUCTION OF OVULATION BY OESTROGENS

1965 ◽  
Vol 33 (3) ◽  
pp. 491-499 ◽  
Author(s):  
F. DÖCKE ◽  
G. DÖRNER
Keyword(s):  
Effective Dose ◽  
Corpus Luteum ◽  
Anterior Pituitary ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Main Site ◽  
Induction Of Ovulation ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Electrolytic Lesions

SUMMARY To study the positive feed-back mechanism by which oestrogen induces corpus luteum formation, electrolytic lesions were placed in different parts of the anterior hypothalamus of prepubertal female rats which were then injected with oestradiol benzoate. Ovarian luteinization did not occur when the main parts of the suprachiasmatic nuclei or of the medial preoptic area had been destroyed. Oestradiol benzoate was implanted stereotaxically into the brain and the anterior pituitary of immature female rats. Whereas 1/25 of the subcutaneously effective dose had to be implanted into the anterior hypothalamus, 1/100 of the peripherally effective dose introduced into the adenohypophysis was sufficient to induce corpus luteum formation in most of the treated animals. The results suggest that, although the anterior hypothalamus is necessary for this positive feed-back mechanism, the anterior pituitary may be the main site of action of oestrogen. Oestrogen may increase the hypophysial sensitivity to the hypothalamic gonadotrophin-releasing factor. Thus an enhanced gonadotrophin secretion may result, sufficient for the induction of ovulation. The possibility is discussed that this positive feed-back mechanism is also essential for the induction of ovulation in women.

THE ROLE OF OESTROGENS IN SPONTANEOUS OVULATION: LOCATION OF SITE OF ACTION OF POSITIVE FEEDBACK OF OESTROGEN BY INTRACRANIAL IMPLANTATION OF THE ANTI-OESTROGEN I.C.I. 46474

1971 ◽  
Vol 50 (2) ◽  
pp. 321-327 ◽  
Author(s):  
J. G. BAINBRIDGE ◽  
A. P. LABHSETWAR
Keyword(s):  
Cerebral Cortex ◽  
Cocoa Butter ◽  
Median Eminence ◽  
Positive Feedback ◽  
Anterior Pituitary ◽  
Site Of Action ◽  
The Brain

SUMMARY In an attempt to locate the site(s) of action of the positive feedback of oestrogen for ovulation, a potent anti-oestrogen, I.C.I. 46474, was stereotaxically implanted into various parts of the brain or into the anterior pituitary. A dose of 5 μg of the anti-oestrogen when implanted into the cerebral cortex or injected subcutaneously on the morning of the day before pro-oestrus in 4-day cyclic rats was only marginally active in interfering with ovulation. By contrast, when the same amount was implanted into the median eminence region or the anterior pituitary, ovulation failed to occur in 80–100% of the rats (P < 0·05). Implantation of the cocoa butter vehicle alone into these regions interfered with ovulation in less than 35% of animals. Introduction of the anti-oestrogen into the anterior hypothalamic or mammillary region gave equivocal results. The data suggest that both the median eminence and the anterior pituitary contain receptors which can be blocked by the anti-oestrogen with resultant inhibition of ovulation. It is concluded that the positive feedback of oestrogen for ovulation is exerted both at the pituitary and the hypothalamic levels.

Effects of gonadal steroid hormones on the hypothalamo-pituitary-liver axis in the control of sex differences in hepatic steroid metabolism in the rat

1982 ◽  
Vol 95 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Agneta Mode ◽  
Gunnar Norstedt
Keyword(s):  
Subcutaneous Injection ◽  
Reductase Activity ◽  
Gonadal Hormones ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Steroid Metabolism ◽  
Male And Female Rats ◽  
Site Of Action ◽  
Hypothalamic Pituitary Axis

The site of action of gonadal hormones in the regulation of hepatic steroid metabolism was investigated by measuring the effects of (i) implantation of oestradiol into the pituitary gland or anterior hypothalamus of males and (ii) subcutaneous injection of a synthetic androgen in deafferentated male and female rats. The hepatic responses measured in vitro were 5α-reduction, and 6β- and 16α-hydroxylation of androstenedione. After intrapituitary or intrahypothalamic implantation of oestradiol, 5α-reductase activity increased and 6β- and 16α-hydroxylase activity decreased in males relative to the enzyme activities of cholesterol-implanted animals, indicating a feminizing effect of the oestrogen. This effect could not be accomplished by subcutaneous injection of the same oestrogen preparation. Deafferentation had no effect on hepatic steroid metabolism in females, but caused a feminization in males. In addition, subcutaneous treatment of intact females with the synthetic androgen caused masculinization of hepatic steroid metabolism, but was without effect in deafferentated animals. Treatment with synthetic androgens had no effect on the hepatic steroid metabolism in deafferentated male animals. Subcutaneous injection of a potent synthetic progestagen had little effect on hepatic steroid metabolism in intact females. It is concluded that oestrogen feminizes hepatic steroid metabolism by an action at the hypothalamic-pituitary level and that an intact hypothalamic-pituitary axis is required for the masculinizing action of the synthetic androgen on hepatic steroid metabolism. It is possible that the site of action of androgens is in the anterior hypothalamus or in adjacent areas of the brain.

Serotonin induces gonadotrophin release through stimulation of LH-releasing hormone release from the median eminence

1986 ◽  
Vol 111 (2) ◽  
pp. 309-315 ◽  
Author(s):  
M. L. Vitale ◽  
M. N. Parisi ◽  
S. R. Chiocchio ◽  
J. H. Tramezzani
Keyword(s):  
Median Eminence ◽  
Anterior Pituitary ◽  
Female Rats ◽  
Male Rats ◽  
Tissue Samples ◽  
Releasing Hormone ◽  
The Third ◽  
Lh Releasing Hormone ◽  
Perifusion System

ABSTRACT The effects of serotonin (5-HT) on the release of gonadotrophins and LH-releasing hormone (LHRH) were examined in an in-vitro perifusion system using median eminences and/or anterior pituitaries obtained from male or pro-oestrous female rats. Animals were killed by decapitation between 12.00 and 13.00 h. A serial double-chamber perifusion system was employed. Three types of experiments were performed. In the first, median eminences were placed in the first chamber and one anterior pituitary in the second chamber. In the second group, only the anterior pituitary was perifused. In the third group, only five median eminences were perifused. In the first and second experiments, LH, FSH and prolactin were determined in the perifusion efflux by radioimmunoassay (RIA). In the third experiment, LHRH was determined by RIA. Addition of 5-HT (final concentrations 0·06, 0·6 and 6·0μmol/l) into the first chamber containing the median eminences stimulated the release of LH and FSH from the pituitary, but did not affect the levels of prolactin in the effluent in the same experiment (prooestrous rats). The stimulatory effect of 5-HT was blocked by the addition of cyproheptadine (1 μmol/l) in the perifusion fluid. The introduction of 5-HT (0·6 μmol/l) into the tube connecting the first and second chambers did not modify the release of LH, nor did 5-HT added to the pituitaries perifused alone. Injection of 5-HT into the first chamber (median eminences), containing tissue samples from male rats, stimulated LH release, but to a significantly (P< 0·001) lower degree than that found when samples from pro-oestrous females were used (P< 0·0001). When median eminences from pro-oestrous rats were perifused alone, injection of 5-HT produced an immediate release of LHRH which peaked during the first 10 min of collection and lasted for 30 min; in these experiments, a clear relationship existed between dose of 5-HT and release of LHRH (P<0·02). The stimulatory effect of 5-HT was blocked by the addition of cyproheptadine (5 μmol/l) or methiothepin (5 μmol/l). These results demonstrate that 5-HT stimulates gonadotrophin release by acting directly on LHRH terminals in the median eminence from pro-oestrous rats. Furthermore, the effect of 5-HT on LHRH release was dose dependent and was nullified by 5-HT receptor blockers (cyproheptadine and methiothepin). J. Endocr. (1986) 111, 309–315

OVULATION IN RABBITS FOLLOWING INTRAVENOUS AND INTRACEREBRAL ADMINISTRATION OF COPPER SULPHATE

1965 ◽  
Vol 50 (4) ◽  
pp. 512-516 ◽  
Author(s):  
Masakuni Suzuki ◽  
Masahiko Hiroi ◽  
Shigehito Sugita
Keyword(s):  
Effective Dose ◽  
Intravenous Injection ◽  
Adult Female ◽  
Median Eminence ◽  
Copper Sulphate ◽  
Induction Of Ovulation ◽  
Posterior Median ◽  
Intracerebral Administration ◽  
Site Of Action

ABSTRACT The present authors (1965) previously reported that the site of action of copper sulphate in the induction of ovulation might be in the vicinity of the posterior median eminence (PME) in the hypothalamus. The authors have now injected a solution of copper sulphate intravenously into adult female Japanese mongrel rabbits and also infused the solution directly into the PME of the hypothalamus. The 50% effective dose for inducing ovulation in some of the rabbits of the tested group was 0.76 μg/kg of copper sulphate in the PME infusion or 3.0 mg/kg in the intravenous injection. This means that the 50% effective dose of copper sulphate required for infusion into the PME is 1/4000 of the 50% effective dose required by intravenous injection.

PITUITARY HORMONE PRODUCTION AND RELEASE IN THE THYROIDECTOMIZED RAT AFTER THYROXINE ADMINISTRATION

1963 ◽  
Vol 42 (2) ◽  
pp. 275-292 ◽  
Author(s):  
A. N. Contopoulos ◽  
A. A. Koneff ◽  
J. D. Jameson
Keyword(s):  
Effective Dose ◽  
Normal Control ◽  
Anterior Pituitary ◽  
Female Rats ◽  
Pituitary Hormone ◽  
Hormone Production ◽  
Minimal Effective Dose ◽  
Thyrotrophic Hormone ◽  
Hormonal Content ◽  
Long Evans

ABSTRACT Female rats of the Long-Evans strain were thyroidectomized at 35–40 days of age and 56 days later were placed into three groups each receiving injections 1, 2 or 3 μg of thyroxine per day for four days. Uninjected thyroidectomized and normal rats were used as controls. Twenty-four hours after the last injection the pituitaries and plasma were bio-assayed as a measure of pituitary hormone production and secretion. The minimal effective dose in hypophysectomized recipients in terms of whole anterior pituitary, or fraction thereof, are as follows: normal control pituitary – TSH, 1/16; FSH, < 3; ICSH, 1; GH> 1/16; thyroidectomy – TSH, 1/8–1/4; FSH, > 5; ICSH, > 5; GH, 3. Thyroxine administration restored the TSH pituitary content to normal at 1 μg dose, and increased it further at the 2 and 3 μg dose. The pituitary content of GH increased from the post-thyroidectomy levels to near normal levels with increasing doses of thyroxine. The ICSH content of the pituitary was influenced by the administration of thyroxine but no effect was obvious in FSH content. GH was not detectable in plasma of thyroidectomized rats but was present in the plasma of animals receiving 2 or 3 μg of thyroxine. Thyrotrophic hormone content of plasma was decreased after administration of thyroxine. Gonadotrophin was not detected in any plasma. The above changes in hormonal content preceded the reappearance of normal pituitary cytology.

OVARIAN STEROID EFFECTS ON GONADOTROPHIN OUTPUT, AND ON THE INCORPORATION OF 35S FROM METHIONINE INTO PROTEIN OF DISCRETE BRAIN AREAS AND THE ANTERIOR PITUITARY

1977 ◽  
Vol 85 (2) ◽  
pp. 279-290
Author(s):  
M. B. ter Haar ◽  
P. C. B. MacKinnon
Keyword(s):  
Luteinizing Hormone ◽  
Median Eminence ◽  
Anterior Pituitary ◽  
Preoptic Area ◽  
Ovarian Hormones ◽  
Female Rats ◽  
Brain Areas ◽  
Lh Surge ◽  
Progesterone Metabolites ◽  
The Brain

ABSTRACT The effects of various ovarian hormones administered on the morning of pro-oestrus on gonadotrophin levels and the incorporation of 35S from methionine into protein of discrete areas of the brain and the anterior pituitary were investigated at 15.00 h of the same day in female rats. The hormones which were investigated in this study could be divided in general into two groups according to their actions. The first group, consisting of oestradiol-17β and progesterone, tended to advance the preovulatory surge of luteinizing hormone (LH) by 3–6 h from 18.00–21.00 h, together with the peaks of [35S] incorporation in the median eminence area and the anterior pituitary which normally accompany the LH surge. The second group, consisting of the LH-stimulated reduced progesterone metabolites, 5α-pregnane-3,20-dione (pregnanedione) and 20α-hydroxypregn-4-en-3-one (dihydroprogesterone), tended to inhibit serum gonadotrophin levels as well as inhibiting the pro-oestrous increase of [35S] incorporation in the median eminence area and in the amygdala, but not in the preoptic area and the anterior pituitary. On the afternoon of pro-oestrus in intact animals, luteinizing hormonereleasing hormone or LH administration had the same effect on [35S]incorporation in the brain as did the progesterone metabolites, though this effect was not observed if the animals had been ovariectomized a few hours beforehand. It is suggested that certain ovarian hormones are involved in the neural events which induce the pre-ovulatory LH surge, while others are associated with neural events which terminate the stimulus for the LH surge.

HYPOTHALAMIC SEXUAL PRECOCITY IN FEMALE RATS OPERATED SHORTLY AFTER BIRTH

1962 ◽  
Vol 41 (2) ◽  
pp. 301-313 ◽  
Author(s):  
S. Horowitz ◽  
J. J. Van der Werff ten Bosch
Keyword(s):  
Anterior Commissure ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Vaginal Opening ◽  
Sexual Precocity ◽  
Paraventricular Nuclei ◽  
Gonadotrophin Secretion ◽  
Electrolytic Lesions

ABSTRACT Electrolytic lesions were placed in the anterior hypothalamus of 3–4 day-old female rats; vaginal opening was hastened in comparison with blank-operated littermates in 12 of 17 rats bearing a lesion in the basal supra-and post-chiasmatic area. In the animals with the earliest vaginal opening, lesions reached upward towards the region of the anterior commissure and the paraventricular nuclei. The degree of advancement of puberty in rats operated at the age of 3 or 4 days was similar to that caused by lesions made at 10, 14 or 15 days. This finding suggests that the effect of a lesion upon gonadotrophin secretion does not begin to take place until after the age of at least two weeks.

THE HYPOTHALAMUS AND PROPYLTHIOURACIL-INDUCED GOITRE IN THE RAT

1963 ◽  
Vol 42 (2) ◽  
pp. 254-262 ◽  
Author(s):  
J. J. van der Werff ten Bosch ◽  
H. E. Swanson
Keyword(s):  
Steady State ◽  
Thyroid Hormone ◽  
Adult Female ◽  
Normal Diet ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Intact Rats

ABSTRACT Adult female rats were given a normal diet, or a diet which contained 0.15% propylthiouracil. At the beginning of the experiment one half of the rats were left intact, whilst the others received an electrolytic basal midline lesion in the anterior hypothalamus. Of each of the four groups of rats, one half was killed after 14 days, the others after 28 days. It was found (both after 14 and after 28 days) that the presence of a lesion reduced the thyroid weight to approximately 75% of the value in intact rats on the same diet, which might be normal or contain propylthiouracil. Propylthiouracil caused thyroid enlargement (to 278% after 14 days and 352–360% after 28 days) in intact rats as compared with intact rats on a normal diet, and in lesioned rats as compared with lesioned rats on a normal diet. It is concluded that lesions cause a lowered steady state of the thyroid-pituitary feed-back system, but that this system responds normally to the alteration of the steady state caused by the propylthiouracil-induced block in thyroid hormone output.

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