THE CORPUS LUTEUM-HYPOPHYSIS RELATIONSHIP: THE EFFECT OF PROGESTERONE TREATMENT ON THE RELEASE OF GONADOTROPHINS IN THE RAT

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.

The administration of progestin or progesterone inhibits oestrus in normal female experimental animals and leads to the cessation of follicular growth (Papanicolaou 1926, working on guinea-pigs; Gley 1928, on rats; Corner 1935, on monkeys). Active testicular extracts or testosterone have a similar effect (Ihrke and D’Amour 1931; Lendle 1931; and Robson 1936, working on rats; Zuckerman 1937, on rhesus monkeys). There is evidence that a phase of luteal activity occurs whenever the ripening of follicles is inhibited (see Evans 1928; Weichert 1930, amongst others), and it was therefore of interest to enquire whether or not luteinization of the ovaries is also an effect of the administration of progesterone and testosterone to normally cyclic female rats. Previous reports on this question are negative. Papanicolaou (1926) observed degenerative changes in the ovaries of guinea-pigs in which several successive oestrous cycles had been suppressed by means of progestin. Selye, Browne and Collip (1936) injected six rats with 4 mg. of progesterone for 12 days, and at the close of the experiment found that neither recent corpora lutea nor mature follicles were present in the ovaries. Albino and black and white rats were used. All injections were given once daily and subcutaneously. Oestrone was administered in aqueous solution, and both progesterone and testosterone propionate in oil. At the end of each experiment the uterus and one of the ovaries were fixed in Bouin’s fluid, and after sectioning, stained with haematoxylin and eosin, the ovary being sectioned serially. The second ovary of each animal was fixed in Flemming’s chrome-osmium fluid with acetic acid, and prepared to show osmicated fats according to the technique described by Deanesly (1930). In certain cases, noted below, the uterus was traumatized by the method of Shelesnyak (1933α) (a modification of that of Long and Evans), in order to produce deciduomata.


1995 ◽  
Vol 145 (3) ◽  
pp. 449-454 ◽  
Author(s):  
J Th J Uilenbroek ◽  
P van der Schoot ◽  
J A M Mattheij ◽  
J J M Swarts

Abstract To study the effects of the antiprogestagen RU486 on luteal activity in pseudopregnant rats, adult female rats made pseudopregnant by sterile copulation were given daily injections with oil vehicle or with RU486 (2 mg/day) either during the entire period of pseudopregnancy (day 1 till day 14) or during the second half of pseudopregnancy (day 8 till day 14). Blood was taken every other day to measure serum concentrations of progesterone. At autopsy, on day 15, the weights of ovaries, isolated corpora lutea and pituitary glands were recorded. In a second study using the same experimental protocol, blood was taken via a jugular vein cannula on days 8, 9, 10 and 11 after induction of pseudopregnancy; on each of these days blood samples were taken at 0700, 0800 and 0900 h, and at 1700, 1800 and 1900 h to measure plasma concentrations of prolactin, LH and progesterone. Administration of RU486 from day 1 of pseudopregnancy onwards had no effect on the increasing concentrations of serum progesterone during the first half of pseudopregnancy. Thereafter progesterone concentrations increased further in RU486-treated rats whereas they decreased in oil-treated pseudopregnant rats. Administration of RU486 from day 8 of pseudopregnancy onwards resulted in a decline in progesterone concentrations in serum on day 10 followed by ovulation on day 11. Plasma LH concentrations in rats treated with RU486 from day 1 of pseudopregnancy were higher than those in oil-treated rats on days 8, 9, 10 and 11. Treatment from day 8 of pseudopregnancy resulted in low LH concentrations at days 8 and 9 and the presence of a preovulatory surge of LH on the afternoon of day 10 (day of pro-oestrus). Plasma concentrations of prolactin measured in oil-treated rats showed two daily surges of similar magnitude in the morning and afternoon of days 8, 9, 10 and 11. In animals treated with RU486 from day 8 onwards, the afternoon surge on day 9 and the morning surge on day 10 were absent. This demonstrated that the luteolytic effect of RU486 when given during the second part of pseudopregnancy is due to a blockade in the afternoon surge of prolactin on day 9. In animals treated with RU486 from day 1 of pseudopregnancy onwards, prolactin in the early morning samples was low, while prolactin in the afternoon samples was highly elevated. At autopsy on day 15, the weights of ovaries, corpora lutea and pituitary glands in animals treated with RU486 from day 1 were larger than those in oil-treated rats; this is in line with an increased secretion of prolactin. In contrast, in animals treated with RU486 from day 8, pituitary weight was not elevated and the increase in ovarian weight was due to the presence of two generations of corpora lutea. In conclusion, whether or not RU486 is luteolytic in pseudopregnant rats depends on the time of administration: injection during the second half of pseudopregnancy inhibits prolactin secretion and induces luteolysis, while administration during the early phase of pseudopregnancy results in high concentrations of prolactin in the early afternoon and therefore prevents luteolysis. Journal of Endocrinology (1995) 145, 449–454


Author(s):  
P. W. Coates ◽  
C. A. Blake ◽  
D. S. Maxwell ◽  
C. H. Sawyer

In rats, physiological studies show that ovariectomy results in a reduced concentration of circulating prolactin. Conversely, ovariectomized rats given estrogen have elevated serum prolactin and increased amounts of prolactin in the anterior pituitary gland. Separate electron microscopic studies suggest modifications in fine structure of prolactin producing (LTH) cells based on relatively large cumulative amounts of estrogen given alone or with comparably high doses of progesterone to adult virgin female or ovariectomized rats. This study was undertaken to provide a correlated morphological and physiological investigation of LTH cells and prolactin levels in a model commonly used by many researchers.Six to seven weeks after bilateral ovariectomy, a group of adult female rats was primed by a subcutaneous injection of 50 ng of estradiol benzoate and 25 mg of progesterone.


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.


1981 ◽  
Vol 88 (3) ◽  
pp. 375-379
Author(s):  
J. DULLAART

Hemipituitary glands of immature female rats, aged 10, 15, 20, 25, 30 and 35 days and either ovariectomized or sham-operated 5 days earlier, were incubated for 2 h in vitro with or without LH releasing hormone. Concentrations of LH and FSH were determined at the end of the incubations in the incubation media and in the hemipituitary glands, and also in the sera collected at the beginning of the incubation experiments. Results showed that in many instances gonadotrophin release was higher after incubation of glands of ovariectomized rats than with glands of control animals. However, these effects of ovariectomy were much smaller than those observed in vivo and were generally absent in rats of less than 20 days of age. It was concluded that ovariectomy may change the secretory characteristics of the gonadotrophic cells of immature rats but that such changes were largely restricted to immature rats older than 20 days.


1970 ◽  
Vol 48 (3) ◽  
pp. 365-371 ◽  
Author(s):  
A. DANON ◽  
C. P. WELLER ◽  
F. G. SULMAN

SUMMARY Treatment of intact or recently (1 day) ovariectomized female rats with 5 mg perphenazine (Trilafon)/kg/day for 5 days resulted in marked lobulo—alveolar differentiation of the mammary glands. Perphenazine failed to stimulate mammogenesis in chronically (12 days) ovariectomized rats, unless they had been primed with oestradiol. However, mammogenic effects in chronically ovariectomized rats were obtained after implantation of minute amounts (2 μg) of oestradiol into the median eminence, or after treatment for 16 days with the non-steroid pituitary gonadotrophin-inhibitor methallibure (ICI 33828; 20 mg/kg/day). Since these latter procedures counteract the gonadotrophin surge after ovariectomy, it would appear that inhibition of gonadotrophin secretion is necessary before prolactin secretion can be stimulated by perphenazine. Castrated male rats responded to perphenazine with lobulo—alveolar differentiation similar to that in intact males. The implications of this difference with regard to the mechanism of pituitary response to gonadectomy are discussed.


1979 ◽  
Vol 80 (3) ◽  
pp. 389-395 ◽  
Author(s):  
P. SÖDERSTEN ◽  
S. HANSEN

The ability of cyclic female rats to show sexual receptivity 24 h after an injection of 2 μg oestradiol benzoate (OB) was lost 24 h after ovariectomy. Exposure of cyclic rats to anti-oestrogen (nitromophene monocitrate) implants 24 h before ovariectomy and OB treatment prevented the latter from inducing sexual receptivity within 24 h of administration. Treatment of ovariectomized rats with constant release implants filled with an oil solution of 15 μg oestradiol/ml had no behavioural effect in itself, but prepared the rats to show lordosis 24 h after administration of OB. Progesterone treatment (4 mg) induced sexual behaviour in cyclic rats on days other than that of the oestrous cycle when the rats are normally receptive. Evidence is presented that a lower level of oestradiol stimulation than that present during pro-oestrus was needed for the induction of sexual receptivity in ovariectomized rats. It is suggested that the low basal level of oestradiol which was present throughout the oestrous cycle was necessary for the induction of sexual receptivity and that an increase in oestradiol stimulation served to increase the behavioural sensitivity to progesterone.


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.


1984 ◽  
Vol 102 (3) ◽  
pp. 287-294 ◽  
Author(s):  
F. Döcke ◽  
W. Rohde ◽  
P. Gerber ◽  
R. Chaoui ◽  
G. Dörner

ABSTRACT The gonadotrophic response to a single injection of oestradiol benzoate (OB) was studied in acutely ovariectomized adult rats during the different stages of a 4-day ovarian cycle. The results showed a sudden decline of the sensitivity to the gonadotrophin-inhibiting effect of OB between metoestrus and dioestrus. This desensitization to the negative oestrogen feedback was probably caused by an oestrogen action on the medial preoptic area (MPOA). In rats ovariectomized and implanted with OB in the MPOA in metoestrus, an s.c. injection of OB on the presumptive day of pro-oestrus did not lower the circulating LH and FSH levels, whereas a clear suppression of gonadotrophin secretion was seen in females implanted with cholesterol in the MPOA or implanted with OB in the hypothalamic ventromedial–arcuate region. Similar findings were obtained in rats which had been ovariectomized 3–4 weeks before implantation. A final experiment demonstrated that bilateral lesioning of the MPOA also reduced the sensitivity to the negative feedback action of oestrogen in long-term ovariectomized rats. In all experiments performed, diminution of the oestrogen-induced inhibition of LH secretion was more marked than that of suppression of FSH secretion. It is proposed that desensitization to the negative oestrogen feedback, probably resulting from an inhibitory oestrogen action on medial preoptic neurones, is a prerequisite for adequate gonadotrophic support of preovulatory follicle maturation in the presence of a continuously rising oestrogen concentration in the blood. J. Endocr. (1984) 102, 287–294


1982 ◽  
Vol 101 (4) ◽  
pp. 501-506 ◽  
Author(s):  
A. A. J. Jenner ◽  
J. de Koning ◽  
G. P. van Rees

Abstract. Inhibin-like activity in steroid-free bovine follicular fluid (bFF) is demonstrated using an in vitro technique with hemi-pituitary glands from intact female (second day of dioestrus) and ovariectomized rats: synthesis as well as basal release of FSH, but not of LH, are inhibited profoundly. The results confirm and extend data from other investigators on the action of inhibin-like material. The effect of the inhibin-like activity is shown to be reversible, as synthesis and the rise of basal release are restored when bFF is withdrawn from the incubation medium. Synthesis of FSH seems to be inhibited earlier than basal release, and it is suggested that the inhibin-like material acts only directly on FSH synthesis. Some possibilities of the mechanisms of action of inhibin-like activity are discussed.


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