Localization of human follicle‐stimulating hormone in the testis

Abstract

Localization of the follicle-stimulating hormone (FSH) molecule and its receptor (FSHR), as well as the role of FSH in Sertoli cell mitosis and maturation, has been demonstrated by several investigators in human and murine testis by detecting the localization of anti-FSH antibodies or [(131)I]-labeled FSH and by detecting FSH receptor (FSHR) mRNA by in situ hybridization, or FSHR by anti-FSHR antibodies. The presence of FSH in germinal cells is controversial or, in humans, excluded. We have investigated the distribution of the human FSH molecule and its receptor in human and mouse testicular cells under different experimental conditions, at the submicroscopical level, by using a better antigenicity conservative procedure. Thus, the distribution of FSH and of the messenger RNA for its receptor in Sertoli cells has now been clarified. In germinal cells, our observations demonstrate the presence of FSH and the FSHR mRNA: the first on the plasma membrane and in endocytotic vesicles, and the second scattered in the cytoplasm. The cells presenting the higher amount of positivity ranged from spermatogonia to spermatocytes, including round spermatids. Penetration was by the endocytosis via membrane vesicles in which the FSHR is present, whereas its messenger is largely present in the cytoplasm and is responsible for the binding and subsequent internalization of the FSH molecule. As a control, human FSH was administered in vitro to the Y1 mouse cell line, which was stably transfected with cDNA for FSHR and devoid of endogenous FSH. The FSH molecule has been localized by monoclonal antibodies on plasma membranes and vesicles, and the FSHR mRNA was found scattered in the cytoplasm after in situ hybridization. We can now conclude that FSH is present in Sertoli cells and in round germinal cells, both expressing the FSHR. FSH penetrates in a similar way in both kinds of cells via endocytosis, and is therefore subsequently localized in the same membranous organelles.

Differential time course of FSH/FSH receptor complex endocytosis within sertoli and germ cells during rat testis development

“…The present study confirms the presence of FSH-R in both Sertoli and germ cells, as previously reported (Bacetti et al, 1998) and demonstrates for the first time that FSH accumulated within membranous cytoplasmic vesicles of an endosomal nature, during a consequent time before its final lysosomal accumulation in Sertoli cells, spermatogonia, and early spermatocytes. Our data also evidence differences in the celerity of the FSH endocytic process between neonatal and adult testicular cells.…”

“…The present findings show that FSH was firstly present on Sertoli cell, spermatogonia, and spermatocyte plasma membranes, and, secondly, internalized by coated pits associated with clathrin, as described for hCG in Leydig cells (Ghinea et al, 1994) and for FSH in testicular endothelial cells (Vu Hai et al, 2004). In a previous study, FSH was detected in vesicular cytoplasmic components but the nature of these structures was not clearly identified (Bacetti et al, 1998). The present findings reveal that these structures could be associated with early endosomes as suggested by morphological criteria (pale content with small associated membranous tails).…”

“…Most of the effects of FSH are cyclically regulated such as receptor mRNA (Heckert and Griswold, 2002), receptor binding (Hermann et al, 2008), and the second messenger pathway (Welsh and Ireland, 1992). It is well recognized that the main target of the hormone is the supporting Sertoli cells (Heckert and Griswold, 2002), since these cells exhibit membranous FSH receptors (Reichert and Dattatreyamurty, 1989) and their proliferation rate is FSH-dependent (Orth, 1984(Orth, , 1986, although other studies reported that germ cells, mostly spermatogonia, can also present FSH receptors (Orth and Christensen, 1978;Bacetti et al, 1998).…”

Increased Testicular Steroid Concentrations in Patients With Idiopathic Infertility and Normal FSH Levels

“…concerning the germ cells development, even though FSH receptors are present the role of FSH is still obscure [1]. The data in infertile men are numerous [3,14,19; for reviews, see 2,35], and several studies have focused on the understanding of human testicular cell functions in vitro [1,17,28,36,40; for review, see 7].…”

“…The data in infertile men are numerous [3,14,19; for reviews, see 2,35], and several studies have focused on the understanding of human testicular cell functions in vitro [1,17,28,36,40; for review, see 7]. Besides the special architecture of the Sertoli cells [10,43], the presence of integrins and cadherins, which are involved in the cell-cell adhesion, has been reported [31].…”