Effects of RU486 in the expression of progesterone receptor isoforms in the hypothalamus and the preoptic area of the rat during postpartum estrus (original) (raw)
Related papers
Role of progesterone receptors during postpartum estrus in rats
Hormones and Behavior, 2011
We studied the role of progesterone receptor (PR) in the display of female sexual behavior during postpartum estrus in rats. Adult female rats were treated with the PR antagonist, RU486 (1.25 and 5 mg), 3 h after parturition and sexual behavior was evaluated throughout the first postpartum day. Estradiol and progesterone serum levels changed during the first 24 h postpartum. The highest estradiol and progesterone levels were found at 9 and 12 h postpartum, respectively. The predominant PR isoform in the hypothalamus and the preoptic area was PR-A during postpartum day. The content of PR-A increased at 6 h postpartum in the hypothalamus and the preoptic area, and decreased in both regions at 9 h. PR-B content only increased in the preoptic area at 12 h postpartum. The highest display of lordotic and proceptive behaviors were found at 12 h postpartum. The treatment with 1.25 and 5 mg of RU486 respectively reduced lordosis by 61% and 92% at 12 h postpartum. These results suggest that PR is essential in the display of postpartum estrus in rats.
Steroids, 2003
The steroid hormone, progesterone, is a central coordinator of all aspects of female reproductive activity. The physiological effects of progesterone are mediated by interaction of the hormone with specific intracellular progesterone receptors (PRs) that are expressed from a single gene as two protein isoforms and that are members of the nuclear receptor superfamily of transcription factors. Analysis of the structural and functional relationships of each isoform using in vitro systems has demonstrated that the PR-A and PR-B proteins have different transcription activation properties when liganded to progesterone. More recently, selective ablation of the PR-A and PR-B proteins in mice had facilitated examination of the contribution of the individual PR isoforms to the pleiotropic reproductive activities of progesterone. Analysis of the phenotypic consequences of these mutations on female reproductive function has provided proof of concept that the distinct transcriptional responses to PR-A and PR-B observed in cell-based transactivation assays are reflected in a distinct tissue-selective contribution of the individual isoforms to the reproductive activities of progesterone. In PR-A knockout mice, in which the expression of the PR-A isoform is selectively ablated (PRAKO), the PR-B isoform functions in a tissue-specific manner to mediate a subset of the reproductive functions of PRs. Ablation of PR-A does not affect response of the mammary gland or thymus to progesterone but results in severe abnormalities in ovarian and uterine function leading to female infertility. More recent studies using PR-B knockout (PRBKO) mice have shown that ablation of PR-B does not affect either ovarian, uterine or thymic responses to progesterone but results in reduced mammary ductal morphogenesis and alveologenesis during pregnancy. Thus, PR-A is both necessary and sufficient to elicit the progesterone-dependent reproductive responses necessary for female fertility, while the PR-B isoform is required to elicit normal proliferative and differentiative responses of the mammary gland to progesterone. This review will summarize our current understanding of the selective contribution of the two PR isoforms to progesterone action.
Role of Progesterone Receptor Isoforms in Female Sexual Behavior Induced by Progestins in Rats
Neuroendocrinology, 2009
was performed in the hypothalamus and preoptic area 24 h after lordosis tests. All progestins induced maximal lordosis 120 min after administration, and antisense oligonucleotides against both PR isoforms inhibited lordosis in all animals. PR-B antisense oligonucleotides also inhibited lordosis induced by progesterone and 5 ␣ -DHP although with less efficacy than total PR antisense oligonucleotides, but the former inhibited lordosis induced by 5  ,3  -Pgl in a similar manner as total PR antisense oligonucleotides. In the hypothalamus and preoptic area, the content of both PR isoforms or PR-B alone was diminished by the administration of total or PR-B antisense oligonucleotides, respectively. These results suggest that the PR-B isoform is essential for the display of the lordosis behavior in rats.
Endocrinology, 1997
Oxytocin (OT) and its receptor (OTR) are synthesized in the endometrium and myometrium of the pregnant rat during late gestation. Both are regulated by estrogen and progesterone (P 4), and tissue concentrations of both increase markedly before parturition. The P 4 antagonist RU486 will induce parturition in the rat. The purpose of the present studies was to investigate changes in OT and OTR messenger RNA (mRNA) and peptide synthesis within the pregnant rat uterus during RU486-induced parturition. Pregnant rats were given a single injection of RU486 (2.5 mg/rat in oil) on day 15 of pregnancy (normal delivery occurs on day 22). Control animals received injections of oil only. Groups of animals (n ϭ 5 in each group) were euthanized at 0, 6, 12, 24, and 48 h after injection and during labor (immediately after delivery of the first pup). Maternal serum estradiol (E 2), P 4 and uterine OT, and PGE 2 concentrations were measured by RIA. Prostaglandin F 2␣ and estrogen receptor levels were measured by enzyme immunoassay (EIA).
Journal of Neurobiology, 2003
Progesterone receptor (PR) plays an important role during sexual differentiation of the rat brain. The objective of the present study was to determine PR protein and gene expression pattern in preoptic-anterior hypothalamic area (POA-AHA) and hypothalamus (HYP), after estradiol or testosterone treatment during the postnatal critical period of sexual differentiation of the rat brain (defeminized animals). Three-day-old female rats were subcutaneously (s.c.) injected with a single dose of 17-estradiol (200 g), or testosterone enanthate (200 g), or vehicle (corn oil). POA-AHA and HYP were dissected 3 h, 24 h, and 14 days, as well as on the day of vaginal opening (VO) after treatments. Other animals, previously treated as above, were acutely injected with 17-estradiol (5 g) on the day of VO; POA-AHA and HYP were obtained 3 h later. Total RNA was extracted and processed for semiquantitative RT-PCR and tissue slices were prepared for protein detection by immunohistochemistry. We observed that PR mRNA expression was increased in POA-AHA and HYP of the animals treated with estradiol or testosterone 3 hours after treatments, compared with the vehicle-treated control group. We also found a significant increase in PR mRNA and protein expression in POA-AHA and HYP on the day of VO in both estradiol and testosterone defeminized rats. Interestingly, the acute administration of estradiol on the day of VO (VO ؉ E 2 ) did not increase PR mRNA or protein expression in POA-AHA and HYP of either estradiol or testosterone defeminized animals, as opposed to the marked induction observed in the intact animals of the control group. The overall results suggest that estradiol and testosterone treatment during the postnatal critical period of sexual differentiation of the brain modifies the regulation of the PR mRNA and protein expression during early onset of maturity.
Neuroscience Letters, 1996
The effects of estradiol benzoate (EB) and progesterone (P4) upon progesterone receptor (PR) gene expression in the cerebral cortex and the hypothalamus of the rabbit were studied. Ovariectomized adult rabbits were subcutaneously treated with EB (25 ~zg/kg) for 2 days, and with EB (25/xg/kg) + a single dose of P4 (5 mg/kg) on day 3. Twenty-four hours after the last dose, the frontal cortex, the hypothalamus and the uterus were excised, total RNA was extracted and processed for reverse transcription-polymerase chain reaction. PR gene expression was induced by EB and down-regulated by P4 both in the frontal cortex and the hypothalamus in a manner similar to that observed in the uterus. The finding that PR gene transcription is regulated by steroid hormones in the cerebral cortex suggests that post-transcriptional processes are involved in the insensitivity of cortical PR protein to steroids regulation previously reported with binding techniques.
Reproductive functions of progesterone receptors
Recent progress in …, 2002
The steroid hormone progesterone plays a central role in the reproductive events associated with pregnancy establishment and maintenance. Physiological effects of progesterone are mediated by interaction of the hormone with specific intracellular progesterone receptors (PRs) that are expressed as two protein isoforms, PR-A and PR-B. Both proteins arise from the same gene and are members of the nuclear receptor superfamily of transcription factors. Since these two isoforms were identified in the early 1970s, extensive controversy has existed regarding the selective contributions of the individual PR proteins to the physiological functions of progesterone. During the past decade, significant progress has been made in this regard using two complimentary approaches. First, analysis of the structural and functional relationships of each isoform using in vitro systems has generated compelling evidence to support the conclusion that PR-A and PR-B have different transcription activation properties when liganded to progesterone. Second, the advent of gene-targeting approaches to introduce subtle mutations into the mouse genome has facilitated the evaluation of the significance of observations made in vitro in a physiological context. Selective ablation of PR-A and PR-B proteins in mice using these technologies has allowed us to address the spatiotemporal expression and contribution of the individual PR isoforms to the pleiotropic reproductive activities of progesterone. Analysis of the phenotypic consequences of these mutations on female reproductive function has provided proof of concept that the distinct transcriptional responses to PR-A and PR-B observed in cell-based transactivation assays are, indeed, reflected in an ability of the individual isoforms to elicit distinct, physiological responses to progesterone. In PR-A knockout mice, in which the expression of the PR-A isoform is selectively ablated (PRAKO), the PR-B isoform functions in a tissue-specific manner to mediate a subset of the reproductive functions of PRs. Ablation of PR-A does not affect responses of the mammary gland or thymus to progesterone but instead results in severe abnormalities in ovarian and uterine function, leading to female infertility. These tissue-selective activities of PR-B are due to this isoform's ability to regulate a subset of progesterone-responsive target genes in reproductive tissues rather than to differences in its spatiotemporal expression relative to the PR-A isoform. More recent studies using PR-B knockout (PRBKO) mice have shown that ablation of PR-B does not affect ovarian, uterine, or thymic responses to progesterone but rather results in reduced mammary ductal morphogenesis. Thus, PR-A is both necessary and sufficient to elicit the progesterone-dependent reproductive responses necessary for female fertility, while PR-B is required to elicit normal proliferative responses of the mammary gland to progesterone. This chapter will summarize recent progress in our understanding of the selective contribution of the two PR isoforms to progesterone action.
Genomic and membrane actions of progesterone: implications for reproductive physiology and behavior
Behavioural brain …, 1999
Progesterone, produced by the ovaries and adrenal glands, regulates reproductive behavior and the surge of luteinizing hormone which precedes ovulation by acting on neurons located in different parts of the hypothalamus. The study of the activation of these reproductive functions in female rats has allowed to explore the different mechanisms of progesterone action in the brain. It has allowed to demonstrate that new actions of the hormone, which have been observed in particular in vitro systems, are also operational in vivo, and may thus be biologically relevant. This mainly concerns the direct actions of progesterone on receptors of neurotransmitters such as oxytocin and GABA. Activation of the progesterone receptor in the absence of ligand by phosphorylation may also play a role.