Molecular and Cellular Biochemistry 278: 185–194, 2005. c ❣ Springer 2005 Effects of follicle-stimulating hormone and vitamin A upon purinergic secretion by rat Sertoli cells Daniel Pens Gelain, Emerson Andr´ e Casali, Ramatis Birnfeld de Oliveira, Luiz Fernando de Souza, Fabiano Barreto, Felipe Dal-Pizzol and Jos´ e Cl´ audio Fonseca Moreira Departamento de Bioqu´ ımica, Instituto de Ciˆ encias B ´ asicas da Sa ´ ude, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil Received 14 February 2005; accepted 18 May 2005 Abstract Follicle-stimulating hormone (FSH) and vitamin A (retinol) are two of the main regulators of the male reproductive system. Recently, it has been described that extracellular purines can affect some important reproductive-related functions in Sertoli cells and germinative cells, by activating specific purinergic receptors. In this work, we report that both FSH and retinol are able to induce changes in the levels of extracellular purines of cultured rat Sertoli cells. FSH induced an increase in adenosine, mainly caused by enhanced ecto-ATPase activity, while retinol increased xanthine and hypoxanthine levels, and decreased uric acid concentration by an unknown mechanism. These data indicate that purinergic signaling may be involved in the control and/or regulation of some of the reproductive-related actions of these hormones. (Mol Cell Biochem 278: 185–194, 2005) Key words: Sertoli, FSH, retinol, extracellular purines, purinoceptors Introduction Purine nucleosides and nucleotides can act as important ex- tracellular messengers, besides their more established role in cellular metabolism [1, 2]. These molecules mediate their ef- fects via triggering of distinct cell surface receptors, named adenosine (or P1) and P2 purinergic receptors [3, 4]. While P1 receptors are activated by adenosine, P2 receptors are trig- gered mainly by ATP. Some works have shown that inosine is also able to trigger A 3 adenosine receptors [5]. P2 receptors can be subclassified into P2Y (G-protein coupled receptors) or P2X (ligand-gated ion channels), and adenosine receptors are subdivided into A 1 ,A 2A ,A 2B , and A 3 , according to their Address for offprints: D. P. Gelain, Departamento de Bioqu´ ımica, UFRGS, Laborat´ orio 25. Rua Ramiro Barcelos 2600 anexo, CEP 90035-003, Porto Alegre, RS, Brazil (E-mail: dgelain@yahoo.com.br) effect on adenylyl cyclase activity, effect on IP 3 turnover, and Ca 2+ mobilization. Many authors have been showing that extracellular purines, such as ATP and adenosine, can modulate cellular processes in the male reproductive system through triggering of purinoceptors. Different subtypes of both adenosine and P2 receptors were detected on Sertoli and germinative cells, and their activation can induce important functional changes in these cells. Sertoli cells express A 1 purinoceptors, recently demonstrated to be essential for acquisition of fertilizing ca- pacity [6]; these receptors couple to a G-inhibitory protein when activated by adenosine, thus leading to inhibition of adenylyl cyclase [7, 8] and participating in the modulation of