Influence of estrogen-progesterone combinations on gonadotropin secretion in castrate female rats(1).
TL;DR: In animals given doses of estradiol that were able to decrease serum FSH and LH below castrate levels, but not to prevent the post-castration rise, the effect of progesterone was dose-dependent.
Abstract: In order to study the effect of progesterone in modulating the secretion of gonadotropins, various doses of progesterone were administered to castrated immature and mature female rats. Progesterone did not prevent the postcastration rise of FSH and LH in these animals. Various amounts of progesterone were then administered to castrated rats that were treated with a constant low dose of estradiol. In animals given doses of estradiol that were able to decrease serum FSH and LH below castrate levels, but not to prevent the post-castration rise, the effect of progesterone was dose-dependent. A very low dose of progesterone lowered serum gonadotropins, an intermediate dose brought about an increase in secretion, and high doses were suppressive. The modifying action of progesterone appears to be dependent upon the level of estrogen, the dose of progesterone, and the time of administration.
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TL;DR: The implantation of Silastic capsules containing Estradiol in oil or crystalline progesterone was used to analyze the physiological role of estradiol and progester one in the control of tonic and cyclic LH secretion in the rat to determine the effect of these hormones during the estrous cycle.
Abstract: The implantation of Silastic capsules containing estradiol in oil or crystalline progesterone was used to analyze the physiological role of estradiol and progesterone in the control of tonic and cyclic LH secretion in the rat. Implants were placed subcutaneously immediately after ovariectomy and blood samples collected 3 or 4 days later. Concentrations of LH, estradiol, and progesterone were measured by specific radioimmunoassays and compared with the levels of these hormones during the estrous cycle. In the absence of any progesterone treatment diestrous concentrations of estradiol (up to 23 pg/ml) were unable to inhibit completely the post-castration rise in serum LH levels. Increasing the serum progesterone concentration to the basal level observed on diestrus day 3 (8 ng/ml) had no effect on tonic LH secretion in the absence of estradiol treatment. However, in the presence of this concentration of progesterone, diestrus day 2 levels of estradiol (13 pg/ml) were effective in inhibiting tonic LH secreti...
275 citations
TL;DR: This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition.
Abstract: Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition.
143 citations
TL;DR: Results show that the actin of RU 486 on the preovulatory gonadotropin surge is due to an antagonism of the action of progesterone on the hypothalamic-pituitary axis, and a role for progestersone in modulating the prevulatory surge of gonadotropic levels and, consequently, ovulation is strongly suggested.
Abstract: The role of progesterone in the regulation of the preovulatory surge in gonadotropins and ovulation was examined in this study by use of a potent antagonist of progesterone, RU 486 (17 beta-hydroxy-11 beta-[4-dimethyl-aminophenyl]-17 alpha- [prop-1-ynyl]estra-4,9-diene-3-one). The immature rat primed with pregnant mare's serum gonadotropin (PMSG) and the cycling adult animal were the models used to verify the role of progesterone. When RU 486 (200 micrograms/rat) was given as a single dose on the morning of proestrus, there was a significant reduction in the preovulatory surge levels of gonadotropins and ovulation in both animal models. Serum progesterone levels in both models at the time of death on the evening of proestrus were unaltered upon treatment with RU 486. RU 486 did not have any effect on gonadotropin levels in immature rats 7 days after castration. These results show that the actin of RU 486 on the preovulatory gonadotropin surge is due to an antagonism of the action of progesterone on the hypothalamic-pituitary axis. Thus, a role for progesterone in modulating the preovulatory surge of gonadotropins and, consequently, ovulation is strongly suggested.
121 citations
TL;DR: The data suggest that P, in the presence of late follicular phase levels of E2, augments the release of LH, may induce therelease of FSH, and further modulates pituitary responsiveness to GnRH.
Abstract: This study was designed to investigate whether the amounts of progesterone (P) normally present at midcycle, when administered to normal women pretreated with estradiol benzoate (E2B), alter the release of LH and FSH. Twelve subjects (four groups of three) were studied during two menstrual cycles. On day 1 of both the initial (E2 control) and a subsequent (study) cycle, each subject received E2B im (2.5 μg/kg/12 h) for a total of seven injections. Twelve hours after the final injection, gonadotropin-releasing hormone (GnRH) was given. In the study cycle, P in oil was added to each of the last three injections of E2B in doses of 1.25 (group I), 2.5 (group II), or 5.0 (group III) mg/12 h, and in one group (IV) in graded doses of 1.25, 2.5, and 5.0 mg/12 h. Estradiol levels were similar in both cycles, with a mean (± SE) of 271 ± 3 pg/ml. During the interval of P administration, mean P levels rose gradually from 0.3 ± 0.02 to 1.3 ± 0.12 ng/ml (mean ± SE of all groups). In the study cycle, an FSH rise occurre...
97 citations
TL;DR: The physiological role of progresterone in the induction of the preovulatory gonadotropin surge has been demonstrated and Corticosteroids appear to play a significant role in the secondary FSH surge on late proestrus and early estrus.
96 citations