Secretory reactions of cultured hypophyseal growth hormone-producing adenoma cells to somatoliberin and somatostatin

Abstract

Somatoliberin stimulates secretion of growth hormone and has no effect on secretion of prolactin in primary cultures of hypophyseal adenoma cells obtained from acromegalic patients. A short-term contact of the cells with somatostatin inhibits secretion of growth hormone, while a long-term contact with this hormone inhibits prolactin production. Somatoliberin abolishes the inhibitory effect of somatostatin on the growth hormone secretion and at high concentrations stimulates it.Key Words: hypophyseal adenoma; growth hormone; prolactin; somatoliberin; somatostatin; cell cultures Generally, hypophyseal tumors producing growth hormone (GH) are benign neoplasms. They consist of adenomatous glandular cells secreting considerable amounts of GH in the circulation, which results in acromegaly, homeostatic disturbances, and serious chronic disease.Secretion of GH is often accompanied by secretion of prolactin (PL). Growth hormone and prolactin are produced by individual cells types (somatotrophs and mammotrophs, respectively) or by the same cells (somatomammotrophs [9]).Phylogenetically, GH and PL originate from the same precursor gene [6], which suggests common mechanisms of production and secretion of these hormones and their interaction at the paracrine and autocrine levels.Increased hormonal production and alterations of receptors associated with lowered inhibitory effect Endocrinology Research Center, Russian Academy of Medical Sciences, Moscow of hypothalamus or formation of abnormal relationships should be accompanied by pathological shifts in hormonal interactions and in the regulation of hormone production.In order to test this hypothesis we studied secretion of GH and PL by hypophyseal adenoma cells from acromegalic patients and the effects of somatoliberin (GH releasing factor) and somatostatin (GH inhibiting factor) and compared them with the effect of thyroliberin, a hypothalamic prolactotropic and thyrotropic regulator. MATERIALS AND METHODSHypophyseal tumor specimens were obtained upon surgery from 6 patients with acromegaly, treated with 0.25% trypsin, and homogenized. The procedure was described in detail elsewhere [3]. Cells were seeded (10 s cells/well) into 96-well plates (Flow), and cultures were grown until confluency in medium 199 containing 10% fetal calf serum and antibiotics at