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Effects of chronic estradiol, progesterone and medroxyprogesterone acetate on hippocampal neurogenesis and adrenal mass in adult female rats

Wiley

Both natural estrogens and progesterone influence synaptic plasticity and neurogenesis within the female hippocampus. However, less is known of the impact of synthetic hormones on hippocampus structure and function. There is some evidence that administration of the synthetic progestin, medroxyprogesterone acetate (MPA) is not as beneficial as natural progesterone and can attenuate estrogen-induced neuroprotection. Although estradiol’s effects have been well studied, little is known about the effects of natural and synthetic progestins alone and in combination with estradiol on adult neurogenesis in the female. In the present study, we investigated the effects of chronic estradiol, progesterone, MPA, and a co-administration of each progestin with estradiol on neurogenesis within the dentate gyrus of adult ovariectomized female rats. Twenty-four hours following a bromodeoxyuridine (BrdU; 200mg/kg) injection, female rats were repeatedly administered with either progesterone (1 or 4 mg), MPA (1 or 4 mg), estradiol benzoate (EB), progesterone or MPA in combination with EB (10<g), or vehicle for 21 days. Rats were perfused on day 22 and brain tissue was analyzed for number of BrdU-labeled and Ki67 (an endogenous marker of cell proliferation)-expressing cells. EB alone and MPA+EB significantly decreased neurogenesis and surviving BrdU-labeled cells in the dorsal region of the dentate gyrus, independent of any effects on cell proliferation. Furthermore, MPA (1mg and 4mg) and MPA+EB treated animals had significantly lower adrenal/body weight ratios, and reduced serum corticosterone (CORT) levels. In contrast, P+EB treated animals had significantly higher adrenal/body weight ratios and 1mg P, P+EB, and EB significantly increased CORT levels. The results of the current study demonstrate that different progestins alone and in combination with estradiol can differentially affect neurogenesis (via cell survival) and regulation of the HPA axis. These findings have implications for women using hormone replacement therapies with MPA for both neuroprotection and stress-related disorders.

Text

2017-10-06

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/63210

Chan, M., Chow, C., Hamson, D.K., Lieblich SE, Galea, L.A.M. (2014). Effects of chronic estradiol, progesterone and medroxyprogesterone acetate on hippocampal neurogenesis and adrenal mass in adult female rats. Journal of Neuroendocrinology [CIHR] 26(6):386-99

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http://creativecommons.org/licenses/by-nc-nd/4.0/