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Neo-natal exposure to estrogenic steroids leads to changes in the expression of genes involved in synaptogenesis: IISc Study

Estradiol (a.k.a. 17β-estradiol) is a steroid hormone and the primary female sex hormone. It regulates the estrous and menstrual reproductive cycles and maintains the female reproductive tissues. It is to be noted that the brain sex differentiation takes place very early during development. While this steroid hormone is essential for the normal functioning of the female reproductive organs, high doses of estradiol or related steroid hormones result in infertility and masculinization. Exactly how this happens at the molecular and cellular level is still not very well known. Recently, a team of scientists at the Indian Institute of Science, Bangalore have demonstrated that some critical changes take place in some of the regions of the brain such as preoptic area (POA) in the rats exposed to estradiol soon after birth.

Regions such as preoptic area (POA), hypothalamus and the pituitary gland of the brain have a major role in the sexual development of an individual. The hypothalamus links the nervous system to the endocrine system via the pituitary gland. The pituitary gland produces, among others, hormones that regulate reproductive cycles. As a part of this study, the team investigated the levels of expression of some genes in the POA following administration of estradiol-17b to newborn rats.

The key trigger to ovulation in mammals is the surge in luteinizing hormone (LH). The cyclical release of LH is a property of the female brain and is permanently erased by perinatal exposure to estradiol. Low dose exposure will impact fertility later in adulthood”, explains Dr. Vijayakumar Govindaraj - one of the researchers on the team. An important observation in the current study is the down-regulation of ER-β in the hypothalamus, the main region of the brain known to be involved in initiating cyclicity, which involves initiation of secretion of the needed hormones at selected intervals by the pituitary, which suggests impairment of the ovulatory process in the E2 treated rats, thereby rendering them infertile, asserts Dr. Vijay.

Estradiol is a common steroid used in treating symptoms of menopause, osteoporosis and ovarian failures and some anti-estrogens are used for cancer treatment. It is important to note that some of the anti-estrogens have also estrogenic activity depending on the dose. Apart from medications, chemicals with estrogenic activity are used in our everyday life; Soy products, personal care products and Teflon-coated pots and pans contain these chemicals. “Bisphenol A (BPA) is used in the production of feeding bottles, epoxy resins, and the linings of soda and soup cans. It can leach from plastic containers/bags into food and beverage products. Studies have shown that BPA has estrogenic properties. “It is known that early BPA exposure impairs the normal development of different endocrine-related tissues and it is important not to use estradiol or compounds with estrogenic activity during pregnancy and/or neonatal period” says Dr. Vijay.

The researchers found a significant decrease in the genes associated with synaptogenesis in POA. Synaptogenesis is a process by which sex differences are established in the brain. This decrease affects learning and memory, ultimately leading to loss of reproductive memory and diminished female sexual behaviour. The study has found a possible mechanism of the effects of estradiol resulting in disruption of the cyclical regulation of hormone secretion by the pituitary, thus causing infertility and altered reproduction behavior. Studying the changes in the genes of the brain is only a part of it, part of this study and we have only observed the changes at the molecular level and we have not investigated behavioural changes which is equally important.

Contact Information:

Prof. A. Jagannadha Rao

INSA Senior Scientist

Department of Biochemistry

Indian Institute of Science, Bangalore

Telephone: +91-80-22932308/23608660

Email: ajrao@biochem.iisc.ernet.in/ajrao2006@gmail.com/ajrao_2000@yahoo.com

Author Information:

N.S. Radhika and Prof. S.K. Sarangi are from the Department of Microbiology and Biotechnology, Bangalore University, Bangalore. Prof A.J. Rao and Dr. Vijayakumar Govindaraj belong to the Department of Biochemistry, Indian Institute of Science, Bangalore. This research work is published in the Life Sciences (2015) Journal under the title “17β-estradiol down-regulates the expression of synaptogenesis related genes in selected brain regions of adult female rats”.