Abstract

Spermatogenesis is a concerted sequence of events during maturation of spermatogonia into spermatozoa. The process involves differential gene-expression and cell-cell interplay regulated by the key endocrine stimuli, i.e., follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-stimulated testosterone. FSH affects independently and in concert with testosterone, the proliferation, maturation and function of the supporting Sertoli cells that produce regulatory signals and nutrients for the maintenance of developing germ cells. Rodents are able to complete spermatogenesis without FSH stimulus, but its deficiency significantly decreases sperm quantity. Men carrying loss-of-function mutation in the gene encoding the ligand (FSHB) or its receptor (FSHR) present, respectively, with azoospermia or suppressed spermatogenesis. Recently, the importance of high intratesticular testosterone concentration for spermatogenesis has been questioned. It was established that it can be completed at minimal intratesticular concentration of the hormone. Furthermore, we recently demonstrated that very robust constitutive FSHR action can rescue spermatogenesis and fertility of mice even when the testosterone stimulus is completely blocked. The clinical relevance of these findings concerns a new strategy of high-dose FSH in treatment of spermatogenic failure.

Highlights

  • Reproduction is controlled by the hormones functional in the hypothalamic-pituitary-gonadal (HPG) axis

  • folliclestimulating hormone (FSH) function is an essential part of the complex HPG axis and its feedback control mechanisms in the regulation of testicular function

  • FSH play a crucial role in determination of the number of Sertoli cells and their capacity to maintain spermatogenesis

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Summary

INTRODUCTION

Reproduction is controlled by the hormones functional in the hypothalamic-pituitary-gonadal (HPG) axis In the male they concern the maintenance of testicular testosterone (T) production and spermatogenesis by the two pituitary gonadotropins, luteinizing hormone (LH) and folliclestimulating hormone (FSH). LH stimulates Leydig cell T production, and FSH stimulates in Sertoli cells, in synergy with T, the production of regulatory molecules and nutrients needed for the maintenance of spermatogenesis. Both T and FSH regulate spermatogenesis indirectly through Sertoli cells. We review this information and describe some of our own studies on genetically modified mice, that reveal some new aspects of these regulatory events. Follicle-Stimulating Hormone and Spermatogenesis challenges the basic principles of the hormonal regulation of spermatogenesis, sheds light on its pathogenetic mechanisms, and offers new leads into its treatment

GENERAL PRINCIPLES OF REGULATION OF SPERMATOGENESIS
FSH IS AN IMPORTANT REGULATOR OF SERTOLI CELL PROLIFERATION
FSH SUPPORTS SPERMATOGENESIS QUANTITATIVELY IN RODENTS
Mouse Mouse
THE CONUNDRUM OF THE ROLE OF FSH DEFICIENCY IN HUMAN SPERMATOGENESIS
EXCESSIVE FSH ACTION HAS MINOR INFLUENCE ON TESTIS DEVELOPMENT AND FUNCTION
SUMMARY AND CLINICAL IMPLICATIONS

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