Role of the Melanocortin System in Gonadal Steroidogenesis of Zebrafish

SIMPLE SUMMARY: Control of reproduction in both males and females is complex, and a number of hormonal systems translate internal and/or external information to the hypothalamic-pituitary-gonadal (HPG) system. The control of reproduction integrates this high-energy demanding event to the internal (stored energy availability) and external (resources availability for progeny) conditions, thus increasing environmental fitting and offspring survival. In this paper, we describe new effects of the melanocortin system on gonadal physiology. Both adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormones (MSHs) modulate gonadal steroid secretion working throughout specific melanocortin receptors expressed in different gonadal cell types. The inhibitory effects of ACTH on gonadotropin-stimulated estradiol secretion seems to be related to the deleterious effects of stress on the female reproductive axis. On the contrary, the physiological involvement of MSH peptides on ovarian gametogenesis as well as the stimulatory effects of ACTH on testicular testosterone production remain unknown and further studies are required to understand melanocortin role on gonadal physiology. ABSTRACT: In teleost, as in other vertebrates, stress affects reproduction. A key component of the stress response is the pituitary secretion of the adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. In zebrafish, Mc2r was identified in male and female gonads, while ACTH has been shown to have a physiological role in modulating reproductive activity. In this study, the hypothesis that other melanocortins may also affect how the zebrafish gonadal function is explored, specifically steroid biosynthesis, given the presence of members of the melanocortin signaling system in zebrafish gonads. Using cell culture, expression analysis, and cellular localization of gene expression, our new observations demonstrated that melanocortin receptors, accessory proteins, antagonists, and agonists are expressed in both the ovary and testis of zebrafish (n = 4 each sex). Moreover, melanocortin peptides modulate both basal and gonadotropin-stimulated steroid release from zebrafish gonads (n = 15 for males and n = 50 for females). In situ hybridization in ovaries (n = 3) of zebrafish showed mc1r and mc4r in follicular cells and adjacent to cortical alveoli in the ooplasm of previtellogenic and vitellogenic oocytes. In zebrafish testes (n = 3), mc4r and mc1r were detected exclusively in germ cells, specifically in spermatogonia and spermatocytes. Our results suggest that melanocortins are, directly or indirectly, involved in the endocrine control of vitellogenesis in females, through modulation of estradiol synthesis via autocrine or paracrine actions in zebrafish ovaries. Adult zebrafish testes were sensitive to low doses of ACTH, eliciting testosterone production, which indicates a potential role of this peptide as a paracrine regulator of testicular function.