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Updated: Aug 17, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Oestrogen replacement in vivo rescues the dysfunction of pituitary somatotropes in ovariectomised aromatase knockout
Ming Yan1, Margaret E E Jones, Maria Hernandez
1Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Abstract:
The mechanism of regulation of growth hormone (GH) secretion by oestrogens and androgens is still controversial. Available data on the action of oestrogens on GH expression and secretion in somatotropes is poorly understood. We previously reported that the aromatase knockout (ArKO) mouse with oestrogen deficiency and excessive androgen levels had dysfunctional somatotropes. In order to clarify the influence of androgen and oestrogen, we investigated the in vivo treatment of ovariectomised (OVX) ArKO mice with exogenous oestradiol (E2) on the mRNA expression of GH, GH-secretagogue receptor (GHS-R), GH-releasing hormone receptor (GHRH-R), pituitary-specific transcription factor (Pit-1), and somatostatin receptors (sst1-5) in pituitary glands. Circulating plasma GH levels were also evaluated. The results showed that ArKO/OVX mice have a low expression of pituitary GH, GHRH-R, GHS-R and Pit-1, and significantly reduced GH levels. Treatment of female ArKO/OVX (E2-deficient without excessive androgen) mice with E2 for 21 days enhanced expression of pituitary GHRH-R and Pit-1 to 151 and 168%, respectively, of that in mice without treatment. E2 treatment increased GH expression and plasma levels in ArKO/OVX mice to levels comparable with those in wild-type female mice. We conclude therefore that long-term E2 replacement rescues the dysfunction of somatotropes in ArKO/OVX mice through increases in expression of GH, GHRH-R, and Pit-1 in the pituitary somatotropes, whereas the level of androgen in this oestrogen-deficient female mouse does not significantly influence the function of somatotropes.
Insights
Oestrogen replacement therapy in oestrogen-deficient mice restored growth hormone (GH) secretion by increasing pituitary GH, GHRH-R, and Pit-1 expression. Androgen levels did not significantly impact somatotrope function in this model.
Area of Science:
- Endocrinology
- Reproductive Biology
- Molecular Endocrinology
Background:
- The regulation of growth hormone (GH) secretion by sex hormones, specifically oestrogens and androgens, remains incompletely understood.
- Previous studies indicated that aromatase knockout (ArKO) mice, characterized by oestrogen deficiency and elevated androgens, exhibit somatotrope dysfunction.
Purpose of the Study:
- To elucidate the distinct roles of oestrogen and androgen in regulating GH secretion.
- To investigate the impact of oestradiol (E2) replacement therapy on pituitary gene expression and GH levels in oestrogen-deficient mice.
Main Methods:
- Ovariectomised (OVX) ArKO mice, lacking endogenous oestrogen, were treated with exogenous E2.
- mRNA expression of GH, GHS-R, GHRH-R, Pit-1, and somatostatin receptors (sst1-5) in pituitary glands was quantified.
- Plasma GH levels were measured.
Main Results:
- ArKO/OVX mice displayed reduced expression of pituitary GH, GHRH-R, GHS-R, Pit-1, and significantly lower circulating GH levels.
- E2 treatment for 21 days increased GHRH-R and Pit-1 expression by 151% and 168%, respectively.
- E2 administration normalized GH expression and plasma GH levels in ArKO/OVX mice.
Conclusions:
- Long-term oestradiol replacement effectively rescues somatotrope dysfunction in oestrogen-deficient female mice.
- The observed rescue is mediated by increased expression of GH, GHRH-R, and Pit-1 in pituitary somatotropes.
- Androgen levels did not exert a significant influence on somatotrope function in this oestrogen-deficient model.
