THE EFFECT OF PROMETHAZINE AND CLOMIPHENE ON GONADOTROPHIN SECRETION IN THE RAT

1971 ◽  
Vol 49 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Y. KOCH ◽  
S. DIKSTEIN ◽  
E. SUPERSTINE ◽  
F. G. SULMAN

SUMMARY Promethazine and promethazine sulphoxide selectively inhibited gonadotrophin secretion in female rats. The effects obtained were: decrease in ovarian weight, reduction in the number of follicles and corpora lutea in the ovary, prolongation of the oestrous cycle and reduced amounts of gonadotrophin-releasing factors in the hypothalamus. Very small doses of clomiphene citrate (1–100 ng/kg) increased gonadotrophin secretion in female rats, as shown by an increase in ovarian weight, increase in the number of corpora lutea, shortening of the oestrous cycle and increased amounts of gonadotrophin-releasing factors in the hypothalamus. Higher doses of clomiphene citrate (1 μg—2 mg/kg) produced the well-known inhibition of gonadotrophin secretion. The possible mechanism of action of these drugs is discussed.

1966 ◽  
Vol 51 (2) ◽  
pp. 231-244 ◽  
Author(s):  
Andrew B. Kaufman ◽  
I. Rothchild

ABSTRACT The effect of progesterone on pituitary gonadotrophin release has been studied in the rat. Castrated female rats bearing ovarian autotransplants, or unilaterally ovariectomized rats, were given 1 to 5 mg of progesterone daily for intervals from 7 to 28 days, and then killed. The ovaries, uteri, and vaginas were examined grossly and microscopically, and the pituitary glands were assayed for total gonadotrophin content by the mouse uterine weight method. Although treatment with 5 mg of progesterone for 28 days inhibited ovulation, it did not prevent Graafian follicle development (determined histologically) or secretory function (evaluated by the presence of vaginal mucification) in either of the animal preparations. Progesterone treatment was associated with a significant elevation of pituitary gonadotrophic potency in the castrated rats bearing ovarian autotransplants, but not in the unilaterally ovariectomized rats. These findings suggest that the tonic rate of gonadotrophin secretion is unaffected by treatment with 5 mg of progesterone daily. The acute discharge of the ovulation inducing hormone complex (probably primarily LH) is, however, inhibited by such a dose of progesterone, and probably accounts for the inhibition of ovulation. The findings also suggest that the amount of progesterone secreted by the functioning corpora lutea during pseudopregnancy in the rat is equivalent in effect to between 2 and 5 mg of progesterone injected once daily.


1964 ◽  
Vol 29 (3) ◽  
pp. 255-NP ◽  
Author(s):  
D. L. PETERSON ◽  
R. A. EDGREN ◽  
R. C. JONES

SUMMARY Removal of the right ovaries of 160–180 g. rats was followed in 2 weeks by a hypertrophy of 55 % of the left ovary. This postoperative growth was prevented by the administration of various natural and synthetic steroidal hormones, which were compared at daily doses estimated to produce a 100 % block of the hypertrophy. The following steroids, together with approximate ED 100, were studied: oestrone, 17·8 μg.; oestradiol-17β, 20·4 μg.; oestriol, 95·5μg.; norethynodrel, 72·5μg.; progesterone, 3630μg.;testosterone, 436 μg.; norethisterone, 479 μg.; norbolethone, 155 μg. At doses above ED 100 the natural oestrogens and norethynodrel produced a secondary cycle of ovarian growth, whereas the Δ4-3-oxosteroids depressed ovarian size further. Hemicastrated rats had histologically normal ovaries which contained larger numbers of corpora lutea than those of the intact controls. All compounds appeared to increase follicular development at the ED 100 level; the higher doses of the oestrogens and norethynodrel stimulated excessive luteinization, whereas the Δ4-3-oxosteroids inhibited luteal development and produced large vesicular and cystic follicles.


1992 ◽  
Vol 134 (1) ◽  
pp. 115-125 ◽  
Author(s):  
R. Webb ◽  
G. Baxter ◽  
D. McBride ◽  
A. S. McNeilly

ABSTRACT Two experiments were carried out during the breeding season in ewes, first to investigate the effects of oral administration of a 3β-hydroxysteroid dehydrogenase (3β-HSD) inhibitor (epostane) on the number of corpora lutea, and secondly to investigate the mechanism through which epostane acts. In the first experiment Dorset Horn ewes were treated orally with 25, 50, 100 or 200 mg epostane twice daily between days 10 and 15 of the oestrous cycle. All doses of epostane resulted in an increase in the number of corpora lutea per ewe, although the response was curvilinear, with the 25 mg dose showing the largest response and the 200 mg group the smallest response. Although there was no difference between groups in the number of ewes showing oestrus, the higher doses of epostane had a detrimental effect on fertility. In the second experiment Welsh Mountain ewes were treated twice daily with 25 mg epostane from day 10 of the oestrous cycle and the ovaries were removed for analysis during either the luteal or the follicular phases. Treatment significantly increased the number of follicles >6 mm in diameter, but significantly reduced in-vitro follicular oestradiol and testosterone production. Despite a marked increase in peripheral inhibin concentrations there was no effect on in-vitro inhibin production. Epostane treatment also caused a significant reduction in peripheral FSH concentrations and an increase in mean LH concentration. The latter was due to an increase in LH pulse frequency during the luteal phase and LH pulse amplitude during the follicular phase. These results confirm that treatment of ewes with epostane orally has a significant effect on follicular steroidogenesis and causes a significant increase in the number of corpora lutea per ewe. This effect on ovulation rate is not via an increase in peripheral FSH concentration, but may be caused by a reduction in follicular steroid activity either directly on the ovary or via an alteration in the pattern of LH secretion. Journal of Endocrinology (1992) 134, 115–125


1982 ◽  
Vol 95 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Patrizia Limonta ◽  
Roberto Maggi ◽  
Luciano Martini ◽  
Flavio Piva

Thermal lesions were placed in the subcommissural organ (SCO) of female rats with normal cycles and long-term ovariectomized rats. In normal female rats SCO lesions disrupted the oestrous cycle in more than half of the animals, the majority of which entered a state of prolonged dioestrus. In these animals, serum gonadotrophin levels were similar to those of rats with regular cycles on day 2 of dioestrus. In animals in which the oestrous cycle was maintained, a delayed LH surge occurred on the day of pro-oestrus and the pro-oestrous FSH surge was absent. The usual increase in FSH on the day of oestrus was present. Lesions in the SCO did not change the high gonadotrophin levels typical of ovariectomized animals. These results suggested that the SCO may play a role in the control of the cyclic but not the tonic release of the gonadotrophins. In particular, it appears that the SCO might be involved in the regulation of the hypersecretion of FSH during the day of pro-oestrus.


1971 ◽  
Vol 51 (2) ◽  
pp. 387-391 ◽  
Author(s):  
B. T. DONOVAN

SUMMARY In an attempt to interfere pharmacologically with the feedback action of oestrogen in the ferret, clomiphene citrate was given to anoestrous animals for 10 days, and to oestrous females for 7 or 14 days, in doses ranging from 10 μg to 1000 μg daily. With the higher doses oestrogenic effects on the uterus were observed, while arrest of follicular development in the ovaries indicated inhibition of gonadotrophin secretion. Enhancement of gonadotrophin secretion in anoestrous females was not encountered, although ovulation in oestrous females was an occasional consequence of treatment with the drug.


1992 ◽  
Vol 132 (1) ◽  
pp. 115-122 ◽  
Author(s):  
J. E. Sánchez-Criado ◽  
J. Th. J. Uilenbroek ◽  
B. Karels

ABSTRACT Administration of the antiprogesterone RU486 (2 mg/day) for 14 days to rats with a 5-day reproductive cycle resulted in an increase in both ovarian and pituitary weight in contrast with rats with a 4-day oestrous cycle. Luteal progesterone production decreased earlier in 4-day than in 5-day cyclic rats. Treatment of 5-day cyclic rats with antiprogesterone from the day of metoestrus onwards resulted in the advancement of the preovulatory prolactin surge by 24 h. Progesterone production by the corpus luteum was, however, not affected, indicating that in 5-day cyclic rats the corpora lutea are still functionally active at the time of the preovulatory surge of prolactin. They become, therefore, stimulated both in size and progesterone production. In contrast, the corpora lutea in 4-day cyclic rats are functionally inactive at the time of the preovulatory surge of prolactin, and prolactin acts luteolytically. In conclusion, the advancement of the preovulatory surge of prolactin by 24 h accounts, at least in part, for the increase in ovarian weight in 5-day cyclic rats after treatment with antiprogesterone. The results of these experiments do not agree with a direct effect of the antiprogesterone RU486 on progesterone secretion by the corpus luteum. Journal of Endocrinology (1992) 132, 115–122


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.


1968 ◽  
Vol 58 (1) ◽  
pp. 101-115 ◽  
Author(s):  
Sidney J. Stolzenberg ◽  
Lloyd C. Faulkner ◽  
William Hansel

ABSTRACT Mature cycling female rats received pituitary autografts beneath the kidney capsule or were hypophysectomized only. Intraperitoneal injections of vasopressin at the level of 3 or 4 IU twice daily into rats with autografts caused an increase in adrenal weights after 45 (P < 0.01) and 70 (P < 0.01) days of treatment. There was an increase in the width of the combined zona fasciculata and reticularis observed after 70 days (P < 0.01). These results were accompanied by a decrease in ovarian weight after 45 (P < 0.01) and 70 (P < 0.01) days of vasopressin treatment. The decrease in ovarian weight was due to histologic regression of corpora lutea. Similar injections of vasopressin into hypophysectomized rats for 45 days were without effect on the ovaries or adrenals. Intraperitoneal injections of 3 or 4 IU oxytocin twice daily for 45 days in rats bearing pituitary autografts had no effect on adrenal weight or histology and caused a non-significant decrease in ovarian weight but had no effect on ovarian histology. However, after 70 days of treatment with oxytocin, there was an increase in adrenal weight (P < 0.01) which could not be attributed to an effect on the zona fasciculata-reticularis. There was a decrease in ovarian weight (P < 0.01), similarly attributable to a regression of the corpora lutea. None of the treatments affected uterine weight or histology or thyroid histology in either rats with pituitary autografts or in animals that were simply hypophysectomized. None of the treatments had any obvious effect on the cytologic appearance of the pituitary graft. It is suggested that effective treatments modified the secretory pattern of pituitary grafts.


1983 ◽  
Vol 97 (1) ◽  
pp. 83-89 ◽  
Author(s):  
P. van der Schoot ◽  
J. Th. J. Uilenbroek

Rats with 5-day ovarian cycles were injected daily with 1 mg bromocriptine. This treatment resulted in a change of cycle length from 5 to 4 days and a rapid increase in ovarian weight. The increase in ovarian weight resulted from the accumulation of large numbers of corpora lutea. Normal numbers of corpora lutea were formed during each cycle but luteal bodies did not disappear subsequently. Luteolysis affected only minor foci of luteal tissue and the majority of luteal tissue remained histologically intact throughout the further period of study. The reduction of cycle length from 5 to 4 days occurred when bromocriptine was administered from the day of ovulation only. If treatment was commenced at a later time during the cycle it was not effective. Treatment with bromocriptine appeared to affect the concentrations of progesterone in the blood during dioestrus. During treatment the rats showed the pattern characteristic for 4-day cycles: typically, the high concentrations of progesterone on the day after metoestrus remained absent. These data suggest (1) that the latter part of the production of progesterone during dioestrus by 'non-functional corpora lutea' is dependent on prolactin and (2) that prolongation of high progesterone production after metoestrus plays an important role in changing the length of the cycle from 4 to 5 days. Treatment with bromocriptine did not significantly affect the rate of maturation of follicles destined for the next ovulation. It is possible that follicular maturation is not among the critical variables which determine whether normal ovulatory cycles will last for 4 or 5 days.


1963 ◽  
Vol 204 (6) ◽  
pp. 1023-1027 ◽  
Author(s):  
B. D. Smith ◽  
J. T. Bradbury

Hypophysectomized or intact immature female rats were given follicle-stimulating hormone (FSH), pregnant mare's serum gonadotrophin (PMS), human chorionic gonadotrophin (HCG), or luteinizing hormone (LH) for 3 days, with or without prior administration of diethylstilbestrol for 2 days. Priming with estrogen augmented the ovarian weight response produced by FSH or PMS in both hypophysectomized and intact animals. In contrast, estrogen pretreatment enhanced ovarian growth in intact rats given HCG or LH, but not in hypophysectomized animals similarly treated. Longer periods of priming also failed to augment the ovarian response to HCG in hypophysectomized rats. The ovaries of intact rats given diethylstilbestrol and FSH contained many corpora lutea, whereas luteinization was never noted in hypophysectomized animals similarly treated. Ovarian weight augmentation in the latter was due to enhanced follicular growth throughout the ovary. Estrogen and HCG produced cystic, luteinized follicles in intact rats, in contrast to the lack of such follicular stimulation in hypophysectomized animals. It is concluded that estrogen increases the ovarian response to gonadotrophins by 1) directly stimulating granulosal proliferation, and 2) effecting the release of endogenous gonadotrophins from the pituitary gland.


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