Both estrogen receptor α and β stimulate pituitary GH gene expression

Dimiter Avtanski, Horacio J. Novaira, Sheng Wu, Christopher J. Romero, Rhonda Kineman, Raul M. Luque, Fredric Wondisford, Sally Radovick

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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) α- and ERβ-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 ERα knockout (sERα-KO) mouse model. Basal pituitary GH, PRL, POU1F1, and ERα mRNA expression levels were lower in sERα-KO mice compared with those in controls; whereas ERβ mRNA levels remained unchanged. E2 and DPN stimulated pituitary GH mRNA expression and serum GH levels in control and sERα-KO ovariectomized mice; however, serum GH levels were unchanged in PPT-treated ovariectomized sERα-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 ERα in the lactotroph, these results support a role for both ERα and ERβ in the transcriptional control of Gh in the somatotroph and illustrate important differences in ER isoform specificity in the anterior pituitary gland.

Original languageEnglish (US)
Pages (from-to)40-52
Number of pages13
JournalMolecular Endocrinology
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Estrogen Receptors
Somatotrophs
Gene Expression
Messenger RNA
Knockout Mice
Prolactin
Estrogens
Lactotrophs
Prolactin Receptors
Anterior Pituitary Gland
Serum
Estradiol
Protein Isoforms
Transcription Factors
Animal Models
Steroids
1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole
propionitrile
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Cite this

Avtanski, D., Novaira, H. J., Wu, S., Romero, C. J., Kineman, R., Luque, R. M., ... Radovick, S. (2014). Both estrogen receptor α and β stimulate pituitary GH gene expression. Molecular Endocrinology, 28(1), 40-52. https://doi.org/10.1210/me.2013-1245
Avtanski, Dimiter ; Novaira, Horacio J. ; Wu, Sheng ; Romero, Christopher J. ; Kineman, Rhonda ; Luque, Raul M. ; Wondisford, Fredric ; Radovick, Sally. / Both estrogen receptor α and β stimulate pituitary GH gene expression. In: Molecular Endocrinology. 2014 ; Vol. 28, No. 1. pp. 40-52.
@article{9815d5597df94ea39e5d065041bd9673,
title = "Both estrogen receptor α and β stimulate pituitary GH gene expression",
abstract = "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) α- and ERβ-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 ERα knockout (sERα-KO) mouse model. Basal pituitary GH, PRL, POU1F1, and ERα mRNA expression levels were lower in sERα-KO mice compared with those in controls; whereas ERβ mRNA levels remained unchanged. E2 and DPN stimulated pituitary GH mRNA expression and serum GH levels in control and sERα-KO ovariectomized mice; however, serum GH levels were unchanged in PPT-treated ovariectomized sERα-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 ERα in the lactotroph, these results support a role for both ERα and ERβ in the transcriptional control of Gh in the somatotroph and illustrate important differences in ER isoform specificity in the anterior pituitary gland.",
author = "Dimiter Avtanski and Novaira, {Horacio J.} and Sheng Wu and Romero, {Christopher J.} and Rhonda Kineman and Luque, {Raul M.} and Fredric Wondisford and Sally Radovick",
year = "2014",
month = "1",
day = "1",
doi = "10.1210/me.2013-1245",
language = "English (US)",
volume = "28",
pages = "40--52",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "1",

}

Avtanski, D, Novaira, HJ, Wu, S, Romero, CJ, Kineman, R, Luque, RM, Wondisford, F & Radovick, S 2014, 'Both estrogen receptor α and β stimulate pituitary GH gene expression', Molecular Endocrinology, vol. 28, no. 1, pp. 40-52. https://doi.org/10.1210/me.2013-1245

Both estrogen receptor α and β stimulate pituitary GH gene expression. / Avtanski, Dimiter; Novaira, Horacio J.; Wu, Sheng; Romero, Christopher J.; Kineman, Rhonda; Luque, Raul M.; Wondisford, Fredric; Radovick, Sally.

In: Molecular Endocrinology, Vol. 28, No. 1, 01.01.2014, p. 40-52.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Both estrogen receptor α and β stimulate pituitary GH gene expression

AU - Avtanski, Dimiter

AU - Novaira, Horacio J.

AU - Wu, Sheng

AU - Romero, Christopher J.

AU - Kineman, Rhonda

AU - Luque, Raul M.

AU - Wondisford, Fredric

AU - Radovick, Sally

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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) α- and ERβ-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 ERα knockout (sERα-KO) mouse model. Basal pituitary GH, PRL, POU1F1, and ERα mRNA expression levels were lower in sERα-KO mice compared with those in controls; whereas ERβ mRNA levels remained unchanged. E2 and DPN stimulated pituitary GH mRNA expression and serum GH levels in control and sERα-KO ovariectomized mice; however, serum GH levels were unchanged in PPT-treated ovariectomized sERα-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 ERα in the lactotroph, these results support a role for both ERα and ERβ in the transcriptional control of Gh in the somatotroph and illustrate important differences in ER isoform specificity in the anterior pituitary gland.

AB - 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) α- and ERβ-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 ERα knockout (sERα-KO) mouse model. Basal pituitary GH, PRL, POU1F1, and ERα mRNA expression levels were lower in sERα-KO mice compared with those in controls; whereas ERβ mRNA levels remained unchanged. E2 and DPN stimulated pituitary GH mRNA expression and serum GH levels in control and sERα-KO ovariectomized mice; however, serum GH levels were unchanged in PPT-treated ovariectomized sERα-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 ERα in the lactotroph, these results support a role for both ERα and ERβ in the transcriptional control of Gh in the somatotroph and illustrate important differences in ER isoform specificity in the anterior pituitary gland.

UR - http://www.scopus.com/inward/record.url?scp=84891499877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891499877&partnerID=8YFLogxK

U2 - 10.1210/me.2013-1245

DO - 10.1210/me.2013-1245

M3 - Article

VL - 28

SP - 40

EP - 52

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 1

ER -

Avtanski D, Novaira HJ, Wu S, Romero CJ, Kineman R, Luque RM et al. Both estrogen receptor α and β stimulate pituitary GH gene expression. Molecular Endocrinology. 2014 Jan 1;28(1):40-52. https://doi.org/10.1210/me.2013-1245