Effect of selective serotonin reuptake inhibitors (SSRIs) versus estradiol administration on anterior pituitary cell population and possible regenerative capacity in ovariectomized adult albino rats

Abstract

Background: Reproductive ageing in women and the hormonal changes that occur during the onset of human menopause have been ascribed solely to ovarian failure and oocyte depletion. However, some studies have shown the central nervous system to be the major regulator of age-related reproductive dysfunction. Moreover, it has been postulated that the pituitary gland plays a key role in the menopausal process. Estradiol is a form of estrogen, a female sex hormone produced by the ovaries. Estradiol is used to treat symptoms of menopause such as hot flashes, and vaginal dryness, burning, and irritation. On the other hand, selective serotonin reuptake inhibitors (SSRIs) ease depression by increasing levels of serotonin in the brain. Aim of work: Thus, it became the aim of the present study, to elucidate the effect of SSRIs versus estradiol in ovariectomized rats on the overall anterior pituitary cell population with special emphasis on the Folliculo-stellate (FS) cells. Material and Methods: Thirty adult female Albino rats, ageing 3-4 months and 140-170 gm body weight were used in the present study. They were divided into 4 groups as follows: Group A (control group): further subdivided into 2 subgroups each including 6 rats. A1: rats were left untreated throughout the experiment. A2: rats were left untreated then received 2ml subcutaneous (s.c.) sesame oil injection daily for one week prior to sacrifice. In the remaining 3 groups (6 rats each), the ovaries were ectomized and rats were left for five months to mimic estrogen-depletion models. Then; Group B: 6 rats were used as an ovariectomy model. Group C: 6 rats received 40µg/kg body weight estradiol by s.c. injection daily for one week prior to sacrifice. Group D: 6 rats received 10mg/kg fluoxetine at a single dose/day by feeding tube for one week prior to sacrifice. Results: In the ovariectomized rats, there was loss of structural organization and an apparent decrease of cell population. Widespread vacuolations and cellular degeneration were also observed. An improved cellular architecture and cell population within pars distalis were seen with the administration of both estradiol and fluoxetine. Semithin sections confirmed these results. Immunostaining for the protein S-100 showed an apparent decrease in the distribution of the protein S-100 expression within the FS cells in ovariectomized rats that was significantly increased in response to estradiol and fluoxetine. Conclusion: Ovariectomized rats revealed degeneration of the anterior pituitary cell population and decreased expression of protein S-100 in the pars distalis indicating decreased population of FS cells. Such effects were reversed by either estradiol or fluoxetine administration. This might suggest the added effect of both drugs if administered together on the improvement of anterior pituitary cell population as well as FC cells.