| First Author | Avtanski D | Year | 2014 |
| Journal | Mol Endocrinol | Volume | 28 |
| Issue | 1 | Pages | 40-52 |
| PubMed ID | 24284820 | Mgi Jnum | J:211885 |
| Mgi Id | MGI:5576842 | Doi | 10.1210/me.2013-1245 |
| Citation | Avtanski D, et al. (2014) Both estrogen receptor alpha and beta stimulate pituitary GH gene expression. Mol Endocrinol 28(1):40-52 |
| abstractText | Although sex steroids have been implicated in the control of mammalian growth, their direct effect on GH synthesis is less clear. The aim of this study was to establish whether estradiol (E2) directly affects GH synthesis in somatotrophs. Somatotroph GH3 and MtT/S cells were used as in vitro models. At physiological doses of E2 stimulation, GH mRNA levels were increased and the ER antagonist ICI 182,780 completely abolished this effect. Estrogen receptor (ER) alpha- and ERbeta-selective agonists, propylpyrazole triol (PPT), and 2,3-bis(4-hydroxyphenyl) propionitrile (DPN), respectively, augmented GH mRNA expression and secretion, whereas E2 and PPT, but not DPN increased prolactin (PRL) mRNA levels. E2, PPT, and DPN stimulated expression of the pituitary transcription factor Pou1f1 and increased its binding to the GH promoter. In vivo evidence of E2 effects on GH synthesis was obtained from the generation of the somatotroph-specific ERalpha knockout (sERalpha-KO) mouse model. Basal pituitary GH, PRL, POU1F1, and ERalpha mRNA expression levels were lower in sERalpha-KO mice compared with those in controls; whereas ERbeta mRNA levels remained unchanged. E2 and DPN stimulated pituitary GH mRNA expression and serum GH levels in control and sERalpha-KO ovariectomized mice; however, serum GH levels were unchanged in PPT-treated ovariectomized sERalpha-KO mice. In these animal models, PRL mRNA levels increased after either E2 or PPT, but an increase was not seen after DPN treatment. Thus, we propose a mechanism by which estrogen directly regulates somatotroph GH synthesis at a pretranslational level. In contrast to the predominant effect of ERalpha in the lactotroph, these results support a role for both ERalpha and ERbeta in the transcriptional control of Gh in the somatotroph and illustrate important differences in ER isoform specificity in the anterior pituitary gland. |
