Stimulatory effect of gonadotropin-releasing hormone (GnRH) on in vitro prolactin secretion and presence of GnRH specific receptors in a subset of human prolactinomas

Abstract

Brandi AM, Barrande G, Lahlou N, Crumeyrolle M, Berthet M, Leblanc P, Peillon F, Li JY. Stimulatory effect of gonadotropin-releasing hormone (GnRH) on in vitro prolactin secretion and presence of GnRH specific receptors in a subset of human prolactinomas. Eur J Endocrinol 1995;132:163–70. ISSN 0804–4643 The purpose of this study was to determine whether gonadotropin-releasing hormone (GnRH) may exert a direct action on human prolactinomas. On a series of 17 adenomas, we studied the effect of GnRH on the in vitro prolactin (PRL) secretion of dispersed and perifused cells of 10 cases and the [125I]GnRH agonist binding on frozen sections of three out of the adenomas studied in perifusion and on the membrane preparations of seven other cases. Two 20-min pulses of GnRH (10−7 mol/l) stimulated the in vitro PRL secretion of three adenomas out of 10 (increase of 200, 444 and 205%, respectively, above basal levels). The GnRH receptors of three adenomas bound GnRH agonist (Des-Gly10-(d-Ala6)-GnRH ethylamide). The binding was specific, with a high affinity (Kd = 0.60, 0.48 and 0.40 nmol/l) similar to that of two human anterior pituitaries obtained post-mortem (Kd = 0.70 and 0.40 nmol/l). Indirect immunoperoxidase revealed that the majority of the cells (60–90%) in all the adenomas studied contained immunoreactive PRL. Four of them also contained cells immunoreactive to the α-subunit of the glycoprotein hormones. In none of the prolactinomas were cells immunoreactive to antiserum of anti-β-luteinizing hormone, anti-β-follicle-stimulating hormone or anti-β-thyrotropin. All the prolactinomas that were responsive to GnRH in perifusion experiments and/or bound specifically to [125I]GnRH agonist were also immunoreactive for α-subunit. These results show that GnRH, via GnRH specific receptors, exerts a stimulation on in vitro PRL secretion in a subset of prolactinomas characterized by the presence of α-subunit. Anne Marie Brandi, Unité INSERM 223, Faculté de Médecine Pitié-Salpêtrière, 105 Boulevard de l'Hôpital, 75013 Paris, France