THE MECHANISM OF THE INDUCTION OF OVULATION BY OESTROGENS

1965 ◽  
Vol 33 (3) ◽  
pp. 491-499 ◽  
Author(s):  
F. DÖCKE ◽  
G. DÖRNER

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.

1968 ◽  
Vol 41 (3) ◽  
pp. 353-362 ◽  
Author(s):  
F. DÖCKE ◽  
G. DÖRNER ◽  
K.-H. VOIGT

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.


1962 ◽  
Vol 41 (2) ◽  
pp. 301-313 ◽  
Author(s):  
S. Horowitz ◽  
J. J. Van der Werff ten Bosch

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.


1997 ◽  
Vol 153 (3) ◽  
pp. 411-421 ◽  
Author(s):  
W Klootwijk ◽  
R D H de Boer ◽  
E Sleddens-Linkels ◽  
S M Cockle ◽  
W W de Herder ◽  
...  

Abstract TRH-like immunoreactivity (TRH-LI) was estimated in methanolic extracts of rat tissues and blood by RIA using antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2, or antiserum 8880, which is specific for TRH (pGlu-His-ProNH2). TRH-LI (determined with antiserum 4319) and TRH (determined with antiserum 8880) contents were 8 and 8 ng/g in brain, 216 and 222 ng/g in hypothalamus, 6·5 and 6 ng/g in pancreas, 163 and 116 ng/g in male pituitary, 105 and 77 ng/g in female pituitary, 1 and 0·1 ng/g in salivary gland, 61 and 42 ng/g in thyroid, 12 and 3 ng/g in adrenal, 3 and 0·3 ng/g in prostate, and 11 and 0·8 ng/g in ovary respectively. Blood TRH-LI (antiserum 4319) and TRH (antiserum 8880) levels were 31 and 18 pg/ml in male rats, and 23 and 10 pg/ml in female rats respectively. Unextracted serum obtained from blood kept for at least 1 h at room temperature no longer contained authentic TRH but still contained TRH-LI (males 20·3 ± 3·1, females 15·9 ± 3·0 pg/ml; means ± s.e.m.). Isocratic reverse-phase HPLC showed that TRH-LI in serum is largely pGlu-Glu-ProNH2 (<EEP-NH2), a peptide previously found in prostate and anterior pituitary. In urine, TRH-LI (antiserum 4319) and TRH (antiserum 8880) levels were 3·21 ± 0·35 and 0·32 ± 0·04 ng/ml in male rats and 3·75 ± 0·22 and 0·37 ± 0·04 ng/ml in female rats respectively (means ± s.e.m.). Anion-exchange chromatography on QAE-Sephadex showed that urine of normally fed rats contains both basic/neutral TRH-LI (b/nTRH-LI) and acidic TRH-LI (aTRH-LI) in a ratio of ≈ 40:60, and further analysis by HPLC indicated that aTRH-LI represents <EEP-NH2. Analysis of food extracts and urine from fasted rats demonstrated that b/nTRH-LI is derived from food particles spilled by the rats during urine collection, while aTRH-LI is endogenously produced. While urinary aTRH-LI levels were higher in female than in male rats (2·99 ± 0·41 vs 2·04 ± 0·20 ng/ml), the daily urinary excretion was similar in both sexes (females 15·6 ± 1·4, males 19·5 ± 2·0 ng/day). Intravenously injected <EEP-NH2 disappeared from serum with a half-life of ≈ 1 h, and was recovered unchanged and quantitatively in urine. In contrast, when <EEP-NH2 was administered with food, only ≈ 0·5% was recovered in urine. The urinary clearance rate of serum TRH-LI amounted to 0·52 ± 0·10 ml/min in males and 0·34 ± 0·05 ml/min in females. In view of the presence of <EEP-NH2 in the anterior pituitary gland, and the regulation of its content in parallel with gonadotrophins, we examined the possibility that serum <EEP-NH2 is of pituitary origin and correlates with gonadotrophin secretion. However, treatments that alter pituitary <EEP-NH2 content and gonadotrophin release had no effect on serum TRH-LI or urinary aTRH-LI. In conclusion, the TRH-like peptide <EEP-NH2 is present in rat serum and is excreted into the urine. Moreover, <EEP-NH2 in serum and urine is not derived from rat food and is probably not of pituitary origin. Journal of Endocrinology (1997) 153, 411–421


1972 ◽  
Vol 55 (3) ◽  
pp. 599-607 ◽  
Author(s):  
B. T. DONOVAN ◽  
A. N. LOCKHART

SUMMARY The release of ovulating hormone after acute treatment with gonadal steroids, or corpus luteum removal on different days of the oestrous cycle, was studied in the guinea-pig. Injection of 25, 50 or 100 μg oestradiol or 2·5 mg progesterone on day 13 of the cycle had no effect upon gonadotrophin secretion as judged by follicular histology, but markedly altered the sizes of the corpora lutea of the previous ovulation. Treatment with oestradiol on day 14 did not elicit gonadotrophin secretion. However, administration of the same hormones to animals given 10 μg oestradiol benzoate 24 h earlier caused ovulation or follicular luteinization. Progesterone (2·5 mg) appeared least effective in stimulating gonadotrophin release; 25 μg oestradiol were more effective when given at 12.00 h than at 24.00 h but treatment with both hormones caused ovulation when given at either time of day. Luteal volumes were not affected. Removal of corpora lutea during the second half of the cycle advanced the time of expected ovulation to day 15 or earlier when the procedure was carried out on days 8 or 9, but not on days 10–13. It is concluded that 4–5 days must elapse between the fall in plasma progesterone level associated with corpus luteum regression and the release of ovulating hormone.


1984 ◽  
Vol 102 (2) ◽  
pp. 133-141 ◽  
Author(s):  
R. Bhanot ◽  
M. Wilkinson

ABSTRACT We have attempted to clarify the physiological involvement of endogenous opiates in the steroid-mediated control of gonadotrophin release. Our studies showed that there was an acute reduction in the inhibitory effects of endogenous opiates on LH and FSH release following gonadectomy in the rat. This was indicated by a significant reduction in the ability of naloxone to stimulate serum LH/FSH levels (sampled at 15 min) in 26-day-old female rats 48 h after ovariectomy. Luteinizing hormone was highly sensitive to the inhibitory effects of the synthetic met-enkephalin analogue, FK 33-824, at this time (sampled at 90 min). An unexpected observation was that long-term absence of gonadal steroids also disrupted the ability of exogenous opiates, FK 33-824 and morphine, to influence LH release. This was seen as an inability of FK 33-824 (1·0 or 3·0 mg/kg) to inhibit LH secretion. The effects of gonadectomy on opiate control of LH occurred at all developmental stages and were not due to a disruption of sexual maturation. Opiate involvement in prolactin secretion did not appear to be adversely affected by an absence of gonadal steroids. Another novel aspect of this work was that the opiatergic component in the control of gonadotrophin secretion could be reinstated in long-term gonadectomized rats by treatment with oestradiol benzoate or testosterone propionate. Similarly, priming with increasing dosages of oestradiol benzoate which resulted in progressively lower LH levels gave larger naloxone responses. This steroid–opiate interdependency suggests that the negative feedback influence of gonadal steroids on LH secretion is conveyed, in part, by hypothalamic opiate peptides. Our results therefore provide a neurochemical basis for gonadal steroid negative feedback. J. Endocr. (1984) 102, 133–141


1977 ◽  
Vol 86 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Norma I. Munaro

ABSTRACT The concentration of norepinephrine and the apparent turnover of norepinephrine in the hypothalamus was studied in castrated rats and after the injection of ovarian steroids. Both parameters were found to vary not only with the hormone treatment, but also with the time of the day. Norepinephrine concentration in the anterior hypothalamus of castrated male and female rats was significantly higher in the afternoon than in the morning, but no statistical difference was observed in the concentration of norepinephrine in the posterior hypothalamus. Three days after the injection of a single dose of 20 μg oestradiol benzoate, norepinephrine concentration and apparent turnover were found with decreased significant values in the anterior hypothalamus of castrated females, killed in the afternoon. Progesterone 2 mg injected three days after the priming dose of oestradiol benzoate, produced 4 h later in the afternoon a significant rise in norepinephrine concentration and apparent turnover. These results suggest that the apparent turnover of hypothalamic norepinephrine in the afternoon is reduced by oestrogen and increased by oestrogen plus progesterone.


1977 ◽  
Vol 85 (2) ◽  
pp. 267-278 ◽  
Author(s):  
K.-J. Gräf ◽  
R. Horowski ◽  
M. F. El Etreby

ABSTRACT The purpose of the present study was to investigate the biological effectiveness of two highly potent prolactin (PRL) inhibitors, lisuride hydrogen maleate (LMH) and 2-Br-α-ergocryptine (CB-154), in the absence of hypothalamic factors acting directly at the level of the anterior pituitary. Hypophysectomized female rats bearing 4 transplanted pituitaries beneath the kidney capsules were treated with oestradiol benzoate (OeB) and progesterone (P) with or without simultaneous administration of LHM or CB-154 for 22 days in order stimulate or inhibit lobulo-alveolar growth of the mammary glands. In addition to the investigation of the mammary glands by DNA determination and assessment of the histological pictures, the aim of this study was directed towards the influence of the substances tested at the level of the anterior pituitary remote from the hypothalmus. In this connection the changes in the different cells within the ectopic pituitaries as revealed by immunoenzyme-cytochemical studies were investigated. The results obtained support the classical view of a neuroendocrine regulation of mammary gland growth and the importance of oestrogens, P and PRL within this system. Both ergot derivatives LHM and CB-154 were able to antagonize the stimulatory effect of OeB combined with P on the mammary gland. With regard to the mechanism of action of LHM and CB-154 it is concluded that both substances act via a direct action on dopaminergic receptors within the ectopic anterior pituitary.


1960 ◽  
Vol XXXIII (IV) ◽  
pp. 569-576 ◽  
Author(s):  
Ronald J. Gellert ◽  
William F. Ganong

ABSTRACT Eight female rats with electrolytic lesions involving the arcuate nucleus in the posterior tuberal region of the hypothalamus matured significantly earlier than unoperated controls. Lesions placed in the anterior hypothalamus, mammillary body, hippocampus, cortex and thalamus of immature female rats had no effect on the age at which vaginal opening and first oestrus occurred.


2003 ◽  
Vol 2003 ◽  
pp. 1-1
Author(s):  
B.V.E. Segwagwe ◽  
K.L. Macmillan ◽  
P.D. Mansell

Oestrous synchronisation involves synchronisation of ovarian follicular turnover, new wave emergence, and finally induction of ovulation which can be achieved with an injection of either GnRH (Pursley et al. 1997)or oestradiol benzoate (ODB) (Day et al. 2000). A comparative study investigating corpus luteum (CL) and follicular emergence after the administration of either GnRH or ODB at pro-oestrus has not been reported. It was hypothesised that the injection of ODB at pro-oestrus would delay emergence of the first post-ovulatory follicular wave, but that CL development and plasma progesterone concentrations would be similar in cows induced to ovulate with either GnRH or ODB.


Author(s):  
B.V.E. Segwagwe ◽  
K.L. MacMillan ◽  
P.D. Mansell

Oestrous synchronization involves synchronization of ovarian follicular turnover, new wave emergence, and finally induction of ovulation. The final step can be synchronized by the parenteral administration of either GnRH or oestradiol benzoate. This study investigated corpus luteum and follicular emergence after ovulation had been induced by the administration of either GnRH or oestradiol benzoate. The injection of oestradiol benzoate may have delayed the emergence of the first follicular wave subsequent to the induced ovulation; administration of oestradiol benzoate or GnRH lowered the progesterone rise so that the maximum dioestrous concentration of progesterone on Day 9 was lower when cows were treated during pro-oestrus compared to the spontaneously ovulating controls. One implication of findings from the present study is that induction of ovulation with either oestradiol benzoate or GnRH, administered 24 or 36 h after withdrawal of the CIDR device, respectively, may lower fertility. Future studies must identify the timing of administration relative to the time of CIDR device withdrawal and the optimum concentration of oestradiol benzoate or GnRH that would not have untoward effects on the development of the corpus lutea, particularly within the first week of dioestrus.


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