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P L Keyes

Publications and source records attributed to P L Keyes.

At least 55 records · Page 3Linked to original sources
PubMed1981

Effects of human chorionic gonadotropin in the rabbit corpus luteum: loss of estrogen receptor and decreased steroidogenic response to estradiol.

The effects of hCG on luteal estrogen receptor and steroidogenesis were examined in 9-day-pseudopregnant rabbits. Twenty-four hours after the injection of ovulatory dosages of hCG (10-100 IU), a dose-related loss of luteal estrogen receptor and in vitro progesterone production was observed. The declining progesterone production was not due to the increased conversion of progesterone to the major metabolite, 20 alpha-dihydroprogesterone. The loss of steroidogenesis induced by hCG was not permanent and could be reversed by estradiol treatment started within 24 h of hCG injection. In those animals with a higher luteal estrogen receptor content at the start of the estrogen treatment, the steroidogenic response was greater. These findings indicate that hCG-induced loss of steroidogenesis is associated with the loss of luteal estrogen receptor. The degree of restoration of progesterone synthesis induced by a 24-h period of estradiol treatment may be related to the content of unoccupied cytoplasmic estrogen receptor in the corpus luteum.

20-alpha-Dihydroprogesterone↗
PubMed1979

Estrogen action in the corpus luteum.

The luteotropic action of estradiol has been studied in the rabbit and rat, and it is proposed that in both species, estradiol may be the "ultimate" luteotropic hormone. The acute dependence of the rabbit corpus luteum upon estradiol is illustrated by the rapid decline in serum progesterone after withdrawal of estradiol (removal of Silastic implant containing 17 beta-estradiol) and by the restoration of serum progesterone to normal values when the estradiol implant is replaced 24 hours later. The identification and characterization of a cytoplasmic and nuclear estrogen receptor in the rabbit corpus luteum and the translocation of the cytoplasmic receptor suggest that estradiol may be acting as it does in other estrogen target tissues. The administration of LH antiserum in pregnant rats causes rapid decreases in luteal estradiol and serum progesterone concentrations, which can be prevented by the administration of low doses of testosterone. This luteotropic effect of testosterone is attributed to an action of estradiol which is formed within the corpus luteum via the luteal aromatase. The rabbit corpus luteum, which has no aromatase, is totally dependent upon estradiol produced by the ovarian follicles and LH is essential to maintain follicular estradiol synthesis. The rat corpus luteum, which is rich in aromatase activity, may produce its own estrogen from an androgen precursor synthesized within the luteal tissue. The essential role of LH may be the stimulation of the synthesis of androgen precursor. As a working hypothesis it is proposed that in these two species LH is necessary to stimulate the synthesis of estradiol which then acts to sustain progesterone secretion.

20-alpha-Dihydroprogesterone↗
PubMed1979

Properties of nuclear and cytoplasmic estrogen receptor in the rabbit corpus luteum: evidence for translocation.

Nuclear and cytoplasmic estrogen receptors have been identified and characterized in the rabbit corpus luteum, and validated methods are described for the measurement of both unoccupied and total estrogen receptor. Binding was specific for the biologically active estrogens. Equilibrium binding analysis of cytoplasmic estrogen receptor yielded saturable, high affinity binding sites with a Kd of 5.4 x 10(-11) M. Two types of binding sites were found in the nuclear fraction: one with high affinity (Kd = 8.9 x 10(-11) M) and low capacity, the other with low affinity (Kd = 2.7 x 10(-8) M) and high capacity. In the presence of 0.4 M KCl, the sedimentation coefficients of nuclear and cytoplasmic estrogen receptors are 3.4S, while the value is 6.8S for cytoplasmic receptor in buffer without KCl. Twenty minutes after an iv injection of 2 micrograms 17 beta-estradiol, the available and total cytoplasmic estrogen receptors were depleted. This depletion was accompanied by concomitant and stoichiometric accumulation of receptor in the nucleus, indicating an apparent translocation of the receptor. In corpora lutea of normal rabbits, approximately 80% of the total nuclear receptor is unoccupied. Evidence is presented to suggest that nuclear receptor sites might be ordinarily occupied with estradiol, but during isolation of the nuclear fraction these sites become available or unoccupied. The identification of nuclear estrogen receptor and the phenomenon of translocation of cytoplasmic receptor to the nucleus suggest a similarity of estrogen action in the rabbit corpus luteum and other estrogen target tissues.

Animals↗
PubMed1978

Role of intraluteal estrogen in the regulation of the rat corpus luteum during pregnancy.

The pronounced aromatizing ability of the rat corpus luteum and the ability of estradiol to maintain luteal function. To examine this hypothesis, rats were treated with either estradiol (100 microgram/day), high or low levels of testosterone via Silastic capsules (20 cm or 1 cm in length), or dihydrotestosterone (20-cm capsule) after hypophysectomy and hysterectomy on day 12 of pregnancy. Hypophysectomy and hysterectomy caused serum progesterone and androgen levels, estradiol concentrations in the corpora lutea, and the content of estradiol receptor in luteal cell nuclei to decrease significantly, and caused the cessation of luteal growth. The daily administration of 100 microgram estradiol or of high levels of testosterone via the 20-cm Silastic capsule increased the estradiol concentration in the corpora lutea dramatically, maintained serum progesterone from day 12 through day 15 at concentrations similar to those in pregnant, sham-operated animals, and increased the nuclear content of estradiol receptor in the corpora lutea. Treatment with the small testosterone capsule maintained the serum androgen and progesterone levels, estradiol concentrations in the corpora lutea, and luteal growth at levels observed in pregnant, sham-operated animals. Treatment with the 20-cm dihydrotestosterone capsule did not sustain progesterone secretion and luteal growth. These results suggest that estrogen formed by aromatization within the corpora lutea may play an important role in the regulation of luteal function during pregnancy in the rat.

Animals↗
PubMed1978

Etiology of anovulation in the immature alloxan-diabetic rat treated with pregnant mare's serum gonadotropin: absence of the preovulatory luteinizing hormone surge.

The effects of alloxan-induced diabetes on ovulation and other ovarian responses were investigated in immature rats injected with PMS gonadotropin (PMSG, 15 IU/100 g) on day 30 of age. Rats were killed on day 32 (presumed proestrus) or on day 33, at which time the oviducts were examined for ova. Ovarian weight gain was similar in control and diabetic rats and Graafian follicles were present in both groups on day 32. None of the diabetic rats ovulated while 96% of the control rats ovulated. Anovulation in diabetic rats could not be attributed to a drug side-effect of alloxan or to a lack of ovarian responsiveness, as 90% of the animals ovulated after treatment with insulin or with hCG (5 IU). Measurements of serum estradiol and LH on the morning of presumed proestrus revealed that concentrations of these hormones were not different in control and diabetic rats. However, measurements of LH in blood samples taken in the afternoon from control rats showed an LH surge, whereas no LH surge was found in diabetic rats. Thus, anovulation in immature diabetic rats treated with PMSG is not caused by an attenuation of ovarian responsiveness or by decreased secretion of estradiol, but rather is due to the loss of the LH surge.

Animals↗
PubMed1977

Development-dependent responses of ovarian follicles to FSH and hCG.

Ovarian follicles removed from immature rats (preantral follicles) and immature rats treated in vivo with follicle stimulating hormone (FSH) (antral follicles) released progesterone in vitro in response to either human chorionic gonadotropin (hCG), hFSH, or DBcAMP in a time- and concentration-dependent fashion. Antral follicles produced approximately 20 times more progesterone than preantral follicles in response to both FSH and hCG at 10(-7) M and approximately 5 times more progesterone in response to 8 X 10(-3) M DBcAMP. After in vitro incubations, follicles were transplanted beneath the kidney capsules of recipient rats to assess their ability to luteinize after hormonal stimulation. Only antral follicles incubated with hCG, hFSH, and DBcAMP formed ectopic corpora lutea. Adenylate cyclase activity in preantral and antral follicle granulosa cells increased in response to both 10 mM KF and 10(-6) M hFSH with no major differences observed between membranes prepared from preantral or antral follicle granulosa cells. These results demonstrate that follicular maturation is associated with major changes in the ability of the granulosa cells to produce progesterone and luteinize in response to hormonal stimulation and that these changes may be, in part, independent of a functional hormone-responsive adenylate cyclase system.

Adenylyl Cyclases↗