Stimulatory effect of gonadotropin-releasing hormone (GnRH) on in vitro prolactin secretion and presence of GnRH specific receptors in a subset of human prolactinomas.
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.
Unité INSERM 223, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
A M
AM
Brandi
G
G
Barrande
N
N
Lahlou
M
M
Crumeyrolle
M
M
Berthet
P
P
Leblanc
F
F
Peillon
J Y
JY
Li
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003470:Culture Media; D005260:Female; D005629:Frozen Sections; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism*; D011869:Radioligand Assay; D011966:Receptors, LHRH / Q000032:analysis*
D003470:Culture Media; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin