PubMed · 14934451
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G MAYER. 1951. [Prolactin, luteotrophic factor].. https://pubmed.ncbi.nlm.nih.gov/14934451/
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Peroxisome proliferator-activated receptors (PPARalpha, PPARbeta/delta and PPARgamma) are a family of nuclear receptors that are activated by binding of natural ligands, such as polyunsaturated fatty acids or by synthetic ligands. Synthetic molecules of the glitazone family, which bind to PPARgamma, are currently used to treat type II diabetes and also to attenuate the secondary clinical symptoms frequently associated with insulin resistance, including polycystic ovary syndrome (PCOS). PPARs are expressed in different compartments of the reproductive system (hypothalamus, pituitary, ovary, uterus and testis). Conservative functions of PPARs in mammalian species could be suggested through several in vivo and in vitro studies, especially in the ovary and during placental development. Several groups have described a strong expression of PPARgamma in ovarian granulosa cells, and glitazones modulate granulosa cell proliferation and steroidogenesis in vitro. All these recent data raise new questions about the biologic actions of PPARs in reproduction and their use in therapeutic treatments of fertility troubles such as PCOS or endometriosis. In this review, we first describe the roles of PPARs in different compartments of the reproductive axis (from male and female gametogenesis to parturition), with a focus on PPARgamma. Secondly, we discuss the possible molecular mechanisms underlying the effect of glitazones on PCOS. Like other 'insulin sensitizer' molecules, such as metformin, glitazones may in fact act directly on ovarian cells. Finally, we discuss the eventual actions of PPARs as mediators of environmental toxic substances for reproductive function.
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Follicle-stimulating hormone (FSH) is a key stimulant for the development of the ovarian follicle, while luteinizing hormone (LH) plays a major role in triggering ovulation and luteinization. Both FSH and LH are glycoprotein hormones that share the same alpha subunit but bind to specific seven transmembrane-domain G coupled receptors located on the cell membrane of the granulosa cells, which comprise the main somatic population of the ovarian follicle. These hormone-receptor complexes may trigger different signaling cascades, but the entire repertoire of genes modulated by these hormones is far from being understood, in particular on the transcriptional level. The development of DNA micro-arrays technique, using the entire genome profile of some mammalian species, allows a global approach and screening of multiple signal transduction pathways. This method opened new insights into the cellular and molecular events that control ovulation and desensitization of the corpus luteum to hyperstimulation by gonadotropic hormones. In addition, this technique permitted the discovery of novel members of the EGF family, such as epiregulin and amphiregulin, that were found to be expressed in the gonadotropin-stimulated cells and were discovered to play a crucial role in the mechanism of ovulation. However, because of the pitfalls in interpreting the data other approaches, for example, Northern blots and RT-PCR must be conducted in parallel to verify the validity of the data.