Bipotential effects of estrogen on growth hormone synthesis and storage in vitro

Increased pulses of serum GH coincide with rising estrogens during the reproductive cycle, suggesting estrogen regulation. However, there is lack of agreement about estrogen's direct effects on the pituitary. Pituitaries from cycling female rats were dispersed and plated for 24 h in defined media containing vehicle or 0.001 - 250 nM 17 beta-estradiol. Estrogen (0.01 - 10 nM) increased the percentages of GH antigen-bearing cells in the anterior pituitary significantly ( 1.3- to 1.6-fold) and 0.01 - 1 nM concentrations also stimulated significant increases in GH mRNA-bearing cells and in the integrated OD for GH mRNA. However, 100 - 250 nM either had no effect or, inhibitory effects on the area of label for GH mRNA. To test estrogen's effects on expression of GHRH receptors, cultures were stimulated with biotinylated analogs of GHRH and target cells detected by affinity cytochemistry. Estrogen increased GHRH target cells in populations from rats in all stages of the cycle tested. Basal expression of GHRH target cells declined at metestrus. Cultures treated with 0 - 1 nM estrogen were then dual labeled for bio-GHRH followed by immunolabeling for GH with the antirabbit IgG-ImmPRESS peroxidase polymer. Over 98% of GH cells bound GHRH and 90 - 96% of GHRH-bound cells contained GH in all treatment groups. Thus, low concentrations of estrogen may stimulate expression of more cells with GH proteins, biotinylated GHRH binding sites, and GH mRNA, whereas high concentrations have no effect, or may reduce GH mRNA. These bipotential effects may help explain the different findings reported in the literature.