Bipotential Effects of Estrogen on Growth Hormone Synthesis and Storagein Vitro

Abstract

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 17beta-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.

Effect of estradiol-17β on follicle-stimulating hormone secretion and egg-laying performance of Japanese quail

“…Studies in women have shown a concomitant rise in serum E 2 concentration and in GH secretion, in the late follicular phase of the normal menstrual cycle (Faria et al, 1992;Ovesen et al, 1998). Similar results were also obtained in sheep (Landefeld and Suttie, 1989;Malven et al, 1995;Scanlan and Skinner, 2002), mice (Yan et al, 2004) and rats (Childs et al, 2005). In a study, female rat pituitary cells were cultured for 24 h in defined media containing vehicle or E 2 in different concentrations.…”

“…In a study, female rat pituitary cells were cultured for 24 h in defined media containing vehicle or E 2 in different concentrations. Addition of lowdose (0.01 to 1 nM or 0.01 to 10 nM) E 2 increased the percentage of GH mRNA-bearing cells, whereas high dose of E 2 (100 to 250 nM) either had no effect or inhibitory effects on the percentage of GH mRNA-bearing cells (Childs et al, 2005). Therefore, E 2 dose dependently increases GH secretion.…”

Estrogen mediated cross talk between the ovary and pituitary somatotrope

“…Our studies sought to address these questions with new dual labeling techniques that identified both receptor activity and hormone activity in pituitary cells (Childs, 2002;Childs et al, 2004). We also designed the estrogen treatment paradigm to include a broad range of concentrations.…”

“…We also designed the estrogen treatment paradigm to include a broad range of concentrations. to test the hypothesis that estrogen's actions might be bipotential (Childs et al, 2004)..We hypothesized that the controversy in the literature might be related to the concentration of estrogen used in the previous studies.…”

“…We then studied effects of exposure to the full dose range of estrogen to learn if its effects varied with the concentration (Childs et al 2004). Pituitaries were taken from normal, cycling female rats during diestrus (which showed, on average, a high expression of ER) and the cells were exposed to 0.001-250 nM water soluble 17β estradiol benzoate (from Sigma) for 24 h. We initially discovered little difference in the enhancing effects of estradiol if given for 15 h -48 h. So, we settled on 24 h as a time for most of the experiments.…”