The maturation of estradiol-negative feedback in female rats: Evidence that the resetting of the hypothalamic 'gonadostat' does not precede the first preovulatory surge of gonadotropins

W. W. Andrews, J. P. Advis, Sergio Ojeda

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Abstract

Several experiments were performed to study the changes in the negative feedback of estradiol on gonadotropin secretion around the time of puberty in the female rat. Ovariectomy of juvenile, first diestrus, or adult animals elevated FSH and LH levels 2 and/or 4 days later. Estradiol administered via Silastic capsules, at several dose levels, was much more effective in preventing the postcastration rise of gonadotropins in juvenile than in the older animals. A dose of estradiol that inhibited gonadotropin levels in juvenile rats, but not in adult animals, maintained preovariectomy serum estradiol levels more efficiently in the adult rats. Therefore, a more rapid removal of estradiol from the blood stream cannot explain its lower effectiveness in suppressing gonadotropin release in adult rats. Estradiol-negative feedback effectiveness remained maximal until the day of first proestrus and decreased markedly on the next day (first estrus), remaining low thereafter. 'Resetting' of the gonadostat to estradiol negative feedback was advanced by inducing precocious puberty by means of hyperprolactinemia, but not by mimicking the periovulatory changes in serum estradiol and progesterone in the absence of an LH surge. Serum progesterone levels were much higher in postpubertal rats than in juvenile animals. Ovariectomy of juvenile rats slightly decreased the already low levels of serum progesterone, but it produced a striking progesterone decrease in postpubertal animals. Quantitative replacement of preovariectomy serum progesterone levels in adult rats, treated with an ineffective dose of estradiol, almost completely restored the prepubertal effectiveness of estradiol in inhibiting LH release and, to a lesser extent, release of FSH. The results indicate that 1) physiological levels of estradiol are much more effective in inhibiting gonadotropin release in prepubertal than in postpubertal animals; 2) a major part of the change in sensitivity to estradiol-negative feedback occurs within 24 h after the first preovulatory surge of gonadotropins; 3) although in prepubertal rats estradiol can suppress gonadotropin release in the presence of very low levels of progesterone, after the first ovulation estradiol effectiveness depends on the presence of elevated but physiological serum levels of progesterone; 4) the abrupt, pubertal decline in sensitivity to estradiol-negative feedback appears to depend upon alterations that occur at both the central nervous system-pituitary unit and the gonads during the hours encompassing the first ovulation. It is postulated, therefore, that in the female rat the resetting of the gonadostat to estradiol-negative feedback is a consequence rather than the trigger of puberty.

Original languageEnglish (US)
Pages (from-to)2022-2031
Number of pages10
JournalEndocrinology
Volume109
Issue number6
StatePublished - 1981
Externally publishedYes

Fingerprint

Gonadotropins
Estradiol
Progesterone
Serum
Ovariectomy
Puberty
Ovulation
Precocious Puberty
Diestrus
Proestrus
Hyperprolactinemia
Estrus
Gonads
Capsules

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{2b51c40da8224440b8b990f542d488e2,
title = "The maturation of estradiol-negative feedback in female rats: Evidence that the resetting of the hypothalamic 'gonadostat' does not precede the first preovulatory surge of gonadotropins",
abstract = "Several experiments were performed to study the changes in the negative feedback of estradiol on gonadotropin secretion around the time of puberty in the female rat. Ovariectomy of juvenile, first diestrus, or adult animals elevated FSH and LH levels 2 and/or 4 days later. Estradiol administered via Silastic capsules, at several dose levels, was much more effective in preventing the postcastration rise of gonadotropins in juvenile than in the older animals. A dose of estradiol that inhibited gonadotropin levels in juvenile rats, but not in adult animals, maintained preovariectomy serum estradiol levels more efficiently in the adult rats. Therefore, a more rapid removal of estradiol from the blood stream cannot explain its lower effectiveness in suppressing gonadotropin release in adult rats. Estradiol-negative feedback effectiveness remained maximal until the day of first proestrus and decreased markedly on the next day (first estrus), remaining low thereafter. 'Resetting' of the gonadostat to estradiol negative feedback was advanced by inducing precocious puberty by means of hyperprolactinemia, but not by mimicking the periovulatory changes in serum estradiol and progesterone in the absence of an LH surge. Serum progesterone levels were much higher in postpubertal rats than in juvenile animals. Ovariectomy of juvenile rats slightly decreased the already low levels of serum progesterone, but it produced a striking progesterone decrease in postpubertal animals. Quantitative replacement of preovariectomy serum progesterone levels in adult rats, treated with an ineffective dose of estradiol, almost completely restored the prepubertal effectiveness of estradiol in inhibiting LH release and, to a lesser extent, release of FSH. The results indicate that 1) physiological levels of estradiol are much more effective in inhibiting gonadotropin release in prepubertal than in postpubertal animals; 2) a major part of the change in sensitivity to estradiol-negative feedback occurs within 24 h after the first preovulatory surge of gonadotropins; 3) although in prepubertal rats estradiol can suppress gonadotropin release in the presence of very low levels of progesterone, after the first ovulation estradiol effectiveness depends on the presence of elevated but physiological serum levels of progesterone; 4) the abrupt, pubertal decline in sensitivity to estradiol-negative feedback appears to depend upon alterations that occur at both the central nervous system-pituitary unit and the gonads during the hours encompassing the first ovulation. It is postulated, therefore, that in the female rat the resetting of the gonadostat to estradiol-negative feedback is a consequence rather than the trigger of puberty.",
author = "Andrews, {W. W.} and Advis, {J. P.} and Sergio Ojeda",
year = "1981",
language = "English (US)",
volume = "109",
pages = "2022--2031",
journal = "Endocrinology",
issn = "0013-7227",
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TY - JOUR

T1 - The maturation of estradiol-negative feedback in female rats

T2 - Evidence that the resetting of the hypothalamic 'gonadostat' does not precede the first preovulatory surge of gonadotropins

AU - Andrews, W. W.

AU - Advis, J. P.

AU - Ojeda, Sergio

PY - 1981

Y1 - 1981

N2 - Several experiments were performed to study the changes in the negative feedback of estradiol on gonadotropin secretion around the time of puberty in the female rat. Ovariectomy of juvenile, first diestrus, or adult animals elevated FSH and LH levels 2 and/or 4 days later. Estradiol administered via Silastic capsules, at several dose levels, was much more effective in preventing the postcastration rise of gonadotropins in juvenile than in the older animals. A dose of estradiol that inhibited gonadotropin levels in juvenile rats, but not in adult animals, maintained preovariectomy serum estradiol levels more efficiently in the adult rats. Therefore, a more rapid removal of estradiol from the blood stream cannot explain its lower effectiveness in suppressing gonadotropin release in adult rats. Estradiol-negative feedback effectiveness remained maximal until the day of first proestrus and decreased markedly on the next day (first estrus), remaining low thereafter. 'Resetting' of the gonadostat to estradiol negative feedback was advanced by inducing precocious puberty by means of hyperprolactinemia, but not by mimicking the periovulatory changes in serum estradiol and progesterone in the absence of an LH surge. Serum progesterone levels were much higher in postpubertal rats than in juvenile animals. Ovariectomy of juvenile rats slightly decreased the already low levels of serum progesterone, but it produced a striking progesterone decrease in postpubertal animals. Quantitative replacement of preovariectomy serum progesterone levels in adult rats, treated with an ineffective dose of estradiol, almost completely restored the prepubertal effectiveness of estradiol in inhibiting LH release and, to a lesser extent, release of FSH. The results indicate that 1) physiological levels of estradiol are much more effective in inhibiting gonadotropin release in prepubertal than in postpubertal animals; 2) a major part of the change in sensitivity to estradiol-negative feedback occurs within 24 h after the first preovulatory surge of gonadotropins; 3) although in prepubertal rats estradiol can suppress gonadotropin release in the presence of very low levels of progesterone, after the first ovulation estradiol effectiveness depends on the presence of elevated but physiological serum levels of progesterone; 4) the abrupt, pubertal decline in sensitivity to estradiol-negative feedback appears to depend upon alterations that occur at both the central nervous system-pituitary unit and the gonads during the hours encompassing the first ovulation. It is postulated, therefore, that in the female rat the resetting of the gonadostat to estradiol-negative feedback is a consequence rather than the trigger of puberty.

AB - Several experiments were performed to study the changes in the negative feedback of estradiol on gonadotropin secretion around the time of puberty in the female rat. Ovariectomy of juvenile, first diestrus, or adult animals elevated FSH and LH levels 2 and/or 4 days later. Estradiol administered via Silastic capsules, at several dose levels, was much more effective in preventing the postcastration rise of gonadotropins in juvenile than in the older animals. A dose of estradiol that inhibited gonadotropin levels in juvenile rats, but not in adult animals, maintained preovariectomy serum estradiol levels more efficiently in the adult rats. Therefore, a more rapid removal of estradiol from the blood stream cannot explain its lower effectiveness in suppressing gonadotropin release in adult rats. Estradiol-negative feedback effectiveness remained maximal until the day of first proestrus and decreased markedly on the next day (first estrus), remaining low thereafter. 'Resetting' of the gonadostat to estradiol negative feedback was advanced by inducing precocious puberty by means of hyperprolactinemia, but not by mimicking the periovulatory changes in serum estradiol and progesterone in the absence of an LH surge. Serum progesterone levels were much higher in postpubertal rats than in juvenile animals. Ovariectomy of juvenile rats slightly decreased the already low levels of serum progesterone, but it produced a striking progesterone decrease in postpubertal animals. Quantitative replacement of preovariectomy serum progesterone levels in adult rats, treated with an ineffective dose of estradiol, almost completely restored the prepubertal effectiveness of estradiol in inhibiting LH release and, to a lesser extent, release of FSH. The results indicate that 1) physiological levels of estradiol are much more effective in inhibiting gonadotropin release in prepubertal than in postpubertal animals; 2) a major part of the change in sensitivity to estradiol-negative feedback occurs within 24 h after the first preovulatory surge of gonadotropins; 3) although in prepubertal rats estradiol can suppress gonadotropin release in the presence of very low levels of progesterone, after the first ovulation estradiol effectiveness depends on the presence of elevated but physiological serum levels of progesterone; 4) the abrupt, pubertal decline in sensitivity to estradiol-negative feedback appears to depend upon alterations that occur at both the central nervous system-pituitary unit and the gonads during the hours encompassing the first ovulation. It is postulated, therefore, that in the female rat the resetting of the gonadostat to estradiol-negative feedback is a consequence rather than the trigger of puberty.

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