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

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 alpha-subunit of the glycoprotein hormones. In none of the prolactinomas were cells immunoreactive to antiserum of anti-beta-luteinizing hormone, anti-beta-follicle-stimulating hormone or anti-beta-thyrotropin. All the prolactinomas that were responsive to GnRH in perifusion experiments and/or bound specifically to [125I]GnRH agonist were also immunoreactive for alpha-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 alpha-subunit.

Stimulation of Combinatorial Expression of Prolactin and Glycoprotein Hormone α-Subunit Genes by Gonadotropin-Releasing Hormone and Estradiol-17β in Single Rat Pituitary Cells during Aggregate Cell Culture

“…Indeed, ␣GSU may have an autocrine role in these PRL cells because it stimulates the development (25,37) and secretory activity of lactotrophs (38). Coexpression of PRL and ␣GSU, but not ␤GSUs, has been found in certain prolactinomas that also express the GnRH receptor in the same cells (39).…”

“…It has recently been shown that treatment of fetal mouse with diethylstilbestrol advanced the first appearance of lactotrophs as early as E14, which is earlier than the first detection of GH (57). The coexpression of PRL and ␣GSU mRNA and its up-regulation by GnRH is interesting in view of the report that part of human prolactinomas also coexpress these two genes in the same cells and that only these tumors were responsive to GnRH in terms of PRL secretion (39).…”

Bihormonal Cells Secreting Both Prolactin and Gonadotropins in Normal Rat Pituitary Cells.

“…Alternatively, it has been shown that paradoxical responses to various stimuli occur in human pituitary tumors in vivo and in vitro [10]. A direct effect of GnRH on human prolactinoma cells and the presence of GnRH receptors on the cell surfaces have recently been reported [11]. GnRHresponding cells which contain GH antigens have been reported to be present in normal rat pituitary cells [ Rabbit antiserum to rat PRL was obtained from UCB-Bioproducts, (Brussels, Belgium), and guinea pig antisera to rat LHJ3 and FSHJ3 were obtained from the National Pituitary Agency (Baltimore, MD).…”