EFFECTS OF SEX STEROIDS ON GROWTH HORMONE PRODUCTION IN CULTURED RAT PITUITARY CELLS

Abstract

Monolayer cultures of rat pituitary tumor cells (GH3) were used to study the effects of different sex steroids on growth hormone (GH) production expressed as the amount of extracellular hormone which accumulated during 24 h. The hormone was measured with a sensitive and specific radioimmunoassay. Estradiol-17.beta. (10-12 mol/l-10-6 mol/l) caused a dose-dependent decrease in GH production with the maximum effect (30% of controls) at 10-10 mol/l. After the cessation of treatment with estradiol-17.beta. [E2] (10-8 mol/l for 7 days), control levels of GH were obtained within 11 days after a transient augmentation of production. Progesterone (10-11-10-6 mol/l) caused a dose-dependent stimulation of GH production and the maximum effect (160% of controls) was observed at 10-6 mol/l. Testosterone (10-6 mol/l) decreased the production of GH to 70% of control values, whereas 5.alpha.-dihydrotestosterone (DHT) had no effect. Cell growth was not affected by any of the sex steroids. Corticosterone (10-6 mol/l) increased GH produciton to about 400% of control values and this effect was inhibited by E2 (10-6 mol/l). The hypothalamic peptides (thyrotropin releasing hormone (TRH) and somatostatin) that depressed GH production did not significantly inhibit the stimulatory effect of corticosterone. When used in combination, the effects of E2 (10-6 mol/l) and TRH (3 x 10-7 mol/l) were additive, which was not the case for the combination E2 (10-6 mol/l) and testosterone (10-6 mol/l). These results suggest different action mechanisms of peptide and steroid hormones on GH production in the GH3 cells. If the properties of the GH3 cells reflect those of normal somatotrophs, the sex steroids may alter GH production at the pituitary level, an influence that may be further modulated by corticoids, TRH and somatostatin.