Gonadotrophin control of testicular germ cell development

Successful and complete male germ cell development is dependent on the balanced, endocrine interplay of the hypothalamus, the pituitary and the testis. The hypothalamus secretes gonadotrophin-releasing hormone in a pulsatile manner which, in turn, elicits the pulsatile release of the gonadotrophins LH and FSH from the pituitary. Luteinizing hormone stimulates spermatogenesis indirectly via testosterone, whereas FSH acts directly on the seminiferous tubules. The synthesis and release of gonadotrophic hormones is under the feedback control of testosterone. Whether other testicular peptides such as inhibin and activin are also involved is not yet clear. Luteinizing hormone/testosterone and FSH are the prime regulators of germ cell development. On their own, these hormones are capable of exerting clear-cut stimulatory effects on the spermatogenic process. However, the quantitative production of spermatozoa generally requires the presence of both LH/testosterone and FSH. Since receptors for androgens and FSH are confined to the somatic cells of the testis, the trophic effects of these hormones on germ cells must be indirect. However, it is not known as yet precisely which genes/factors mediate the beneficial effects of androgens and FSH on spermatogenesis. The gonadotrophic hormones have been found in a number of isoforms and multiple transcripts of the LH and FSH receptor have been detected. Therefore, the possibility must be considered that certain forms of male infertility could be due to dysfunctional hormones and/or mutated receptors.