Studies in Zebrafish Reveal Unusual Cellular Expression Patterns of Gonadotropin Receptor Messenger Ribonucleic Acids in the Testis and Unexpected Functional Differentiation of the Gonadotropins

Abstract

This study aimed to improve, using the zebrafish model, our understanding of the distinct roles of pituitary gonadotropins FSH and LH in regulating testis functions in teleost fish. We report, for the first time in a vertebrate species, that zebrafish Leydig cells as well as Sertoli cells express the mRNAs for both gonadotropin receptors (fshr and lhcgr). Although Leydig cell fshr expression has been reported in other piscine species and may be a common feature of teleost fish, Sertoli cell lhcgr expression has not been reported previously and might be related to the undifferentiated gonochoristic mode of gonadal sex differentiation in zebrafish. Both recombinant zebrafish (rzf) gonadotropins (i.e. rzfLH and rzfFSH) stimulated androgen release in vitro and in vivo, with rzfFSH being significantly more potent than rzfLH. Forskolin-induced adenylate cyclase activation mimicked, whereas the protein kinase A inhibitor H-89 significantly reduced, the gonadotropin-stimulated androgen release. Therefore, we conclude that both FSH receptor and LH/choriogonadotropin receptor signaling are predominantly mediated through the cAMP/protein kinase A pathway to promote steroid production. Despite this similarity, other downstream mechanisms seem to differ. For example, rzfFSH up-regulated the testicular mRNA levels of a number of steroidogenesis-related genes both in vitro and in vivo, whereas rzfLH or human chorionic gonadotropin did not. Although not fully understood at present, these differences could explain the capacity of FSH to support both steroidogenesis and spermatogenesis on a long-term basis, whereas LH-stimulated steroidogenesis might be a more acute process, possibly restricted to periods during which peak steroid levels are required.

Sertoli cell proliferation in the adult testis is induced by unilateral gonadectomy in African catfish

“…Irrespective of the mechanism(s) involved, our This has been shown in Japanese eel [31], African catfish [17], and zebrafish [18]. Indeed, Fsh was 23 more potent as steroidogenic hormone than Lh in both catfish [60] and zebrafish [18]. Moreover, Fsh…”

“…but not Lh was able to up-regulate the expression of steroidogenesis related genes in juvenile eel 25 [24] and in adult zebrafish testis [18]. Therefore, we propose that Fsh, rather than Lh, mediated the 26 up-regulation of the steroidogenic capacity of the testis remaining after ULG.…”

Cyp17a1 and Cyp19a1 in the zebrafish testis are differentially affected by oestradiol

“…It can be hypothesized that only in Leydig cells there is an appropriate cellular context for transcriptional inhibition by E 2 . Another hypothesis is that E 2 exerts a negative feedback on the brain/pituitary system, resulting in a reduced gonadotropin release and consequently a fading stimulation of cyp17a1 gene expression and Cyp17a1 synthesis in Leydig cells that, in contrast to germ cells, express receptors for both Fsh and Lh in fish (Garcia-Lopez et al 2010).…”

CARACTERIZACIÓN BIOLÓGICA DE LAS GONADOTROFINAS DE LUBINA (Dicentrarchus labrax) Y DESARROLLO DE HERRAMIENTAS BIOTECNOLÓGICAS E INMUNOLÓGICAS PARA SU ESTUDIO

“…These different responses could be based on the developmental stage of the gonadal tissue, and therefore in the presence of the corresponding GTH receptors. In zebrafish it has been suggested that the higher levels of fshr expression could explain the higher potency of Fsh [57]. In our study, the cultured testes were in late spermatogenesis, and there is no difference in GTH receptor expression at that gonadal stage [59].…”

“…In coho salmon, Lh was progressively more potent than Fsh in stimulating 11-KT production as spermatogenesis progressed through stage IV [56]. However, in zebrafish and channel catfish, recombinant Fsh was more effective in stimulating androgen release than Lh [49,57]; and in African catfish testis, the amount of Fsh needed to obtain a significant steroid release was lower than that of Lh [58]. These different responses could be based on the developmental stage of the gonadal tissue, and therefore in the presence of the corresponding GTH receptors.…”