Bone Morphogenetic Proteins (BMPs): nouveaux modulateurs de la synthèse et de la libération de l'hormone folliculo- stimulante (FSH)

Abstract

Reproductive function requires the secretion of the gonadotropins, luteinizing hormone (LH) and follicle -stimulating hormone (FSH) synthesized by the gonadotrope cells. A tight control of the production of these hormones is crucial, particularly in females, to coordinate the terminal follicular growth, the follicle selection as well as the timing and the number of ovulation. Synthesis and release of both gonadotropins are controlled by hypothalamic gonadotropin releasing hormone (GnRH) and gonadal steroids (progesterone and oestradiol). Despite these common regulators, divergences in the circulating patterns of LH and FSH are often encountered. Such divergences have suggested that other factors are specifically implicated in the control of FSH production. Inhibins and activins, members of the Transforming Growth Factor -Beta (TGF -(3) superfamily, inhibit and stimulate respectively FSH synthesis and release. These gonadal factors are also produced in the pituitary where they act as paracrine factors. Other molecules of the TGF -13 superfamily, the Bone Morphogenetic Proteins (BMPs) have recently been involved for their action in reproduction at ovary level. Whether BMPs act at pituitary level and participate with other factors to regulate FSH production in females is not elucidated. In order to extend our knowledge of the differential regulation of FSH and LH synthesis, this question was addressed in this study and developed around three purposes:ped around three purposes: - Are BMPs and receptors expressed in pituitary? What are their effects on gonadotropin production? Does the natural mutation of BMPR -IB in ewes have an effect at pituitary level?- What are the mechanisms of BMPs action at intracellular level?- Is the mouse gonadotrope cell line LΒT₂ a good model to analyse BMP action on FSH production?Answering to these questions should help to better understand the mechanisms which control the fertility in females.Before presenting the results, some data concerning the gonadotropins and the differential control of their synthesis and release are developed followed by a focus on BMP effects on reproduction. The mechanisms of action of BMPs, as well as activin are also detailed

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