FSH and testosterone signaling in Sertoli cells

Abstract

Testosterone and follicle-stimulating hormone (FSH) are required to obtain full reproductive potential. In the testis, somatic Sertoli cells transduce signals from testosterone and FSH into the production of factors that are required by germ cells as they mature into spermatozoa. Recent advances in identifying new signaling pathways that are regulated by FSH and testosterone have allowed for refinement in the understanding of the independent, overlapping and synergistic actions of these hormones. In this review, we discuss the signaling pathways that are regulated by FSH and testosterone as well as the resulting metabolic and gene expression changes that occur as related to Sertoli cell proliferation, differentiation and the support of spermatogenesis.Reproduction (2005) 130 15-28

Sertoli Cell-specific Expression of Metastasis-associated Protein 2 (MTA2) Is Required for Transcriptional Regulation of the Follicle-stimulating Hormone Receptor (FSHR) Gene during Spermatogenesis

“…Together with our findings that Ar interacted with MTA2 via its LBD in response to androgen stimulation, it is possible that as an important HDAC recruiter and a transcriptional cofactor, MTA2 may directly participate in the regulation of Ar activity because gene expression is usually tightly controlled by the balance between acetylation and deacetylation (34). Testosterone actions present an interesting paradox in that numerous genes and proteins are up-regulated in response to stimulation, but few genes have been characterized that are known to be induced with this steroid through the classical mechanism of Ar binding to specific promoter elements (4). Similarly, we did not detect any androgen response elements in the MTA2 promoter region (data not shown).…”

“…Since the first description of the Sertoli cell (SC) 4 in 1865, this cell has drawn much attention of researchers because it is the only somatic type possessing a close structural relationship with germ cells inside seminiferous tubules (1). The SC serves as a principal structural element to maintain the integrity of the impermeable and immunological blood-testis barrier, provide structural support, and secrete diverse functional glycoproteins and peptides in favor of normal germ cell development and maturation (2).…”

“…FSH and testosterone induce phosphorylation of ERK kinase to similar levels, but FSH is about 2-fold more effective in phosphorylating CREB. Moreover, FSH and testosterone can both stimulate the level of Ca 2ϩ (4). Nevertheless, the mechanisms whereby integration of these two path-ways regulates reproductive function probably involve actions at different levels and remain to be fully established.…”

“…Signaling-Within seminiferous tubules, SCs are the only cell types that possess receptors for testosterone and FSH, and thus these cells are the major targets of both hormonal signals that regulate spermatogenesis (4). To this end, we were interested to know whether MTA2 functions in the crosstalk between these two pathways.…”

Contribution of Recent Transgenic Models and Transcriptional Profiling Studies to Our Understanding of the Mechanisms by which Androgens Control Spermatogenesis

“…FSH affects spermatogenesis via the Sertoli cells which are widely accepted to be the only cells in the testis endowed with FSH receptors [7,8]. FSH plays a very important role in pre-and peripubertal Sertoli cell proliferation [9] and in this way it is a key determinant of spermatogenic capacity in adult life [2,10].…”