Opposite effects of dihydrotestosterone and estradiol on apoptosis in the anterior pituitary gland from male rats

Abstract

Hormones locally synthesized in the anterior pituitary gland are involved in regulation of pituitary cell renewal. In the pituitary, testosterone (T) may exert its actions per se or by conversion to dihydrotestosterone (DHT) or 17β-estradiol (E2) by 5α-reductase and aromatase activity, which are expressed in this gland. Previous reports from our laboratory showed that estrogens modulate apoptosis of lactotropes and somatotropes from female rats. Now, we examined the in vitro and in vivo effects of gonadal steroids on apoptosis of anterior pituitary cells from adult male rats. T in vitro did not modify apoptosis in anterior pituitary cells from gonadectomized (GNX) male rats. DHT, a non-aromatizable androgen, exerted direct antiapoptotic action on total anterior pituitary cells and folliculo-stellate cells, but not on lactotropes, somatotropes, or gonadotropes. On the contrary, E2 exerted a rapid apoptotic effect on total cells as well as on lactotropes and somatotropes. Incubation of anterior pituitary cells with T in presence of Finasteride, an inhibitor of 5α-reductase, increased the percentage of TUNEL-positive cells. In vivo administration of DHT to GNX rats reduced apoptosis in the anterior pituitary whereas E2 exerted proapoptotic action and reduced cells in G2/M-phase of the cell cycle. In summary, our results indicate that DHT and E2 have opposite effects on apoptosis in the anterior pituitary gland suggesting that local metabolization of T to these steroids could be involved in pituitary cell turnover in males. Changes in expression and/or activity of 5α-reductase and aromatase may play a role in the development of anterior pituitary tumors.

Estrogen suppresses bcl2 expression through dnmt1 in Japanese eel ovarian follicle

“…Accumulating evidence suggests that estrogen plays multiple physiological roles in cellular biology, including apoptosis (Ying 2000, Jaita et al 2005, Zarate et al 2009, Magri et al 2016. Jaita et al demonstrated that E 2 induces apoptosis of anterior pituitary lactotropes by upregulating the Fas/FasL system (Jaita et al 2005).…”

Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas

“…In the male, 17β-estradiol exerts rapid apoptotic action in lactotropes, somatotropes, or gonadotropes cells of pituitary gland. However, the effects of gonadal steroids on the expression of Bcl-2 and BAX, in the anterior pituitary gland of male rats, have not been modified [ 93 ].…”

“…The in vitro and in vivo expression of aromatase is in the lactotroph cell of male rats and is involved in the control of proliferation and prolactin release by transforming testosterone to estradiol [ 41 ]. Moreover, the pituitary aromatase activity could be involved in the regulation of the apoptosis of pituitary cells [ 93 ]. Other studies have shown that, in patients with acromegaly and prolactinoma, aromatase was high, was negatively correlated with Ki-67 score, and was higher in the pituitary of patients with complete postoperative remission than without remission [ 12 ].…”

Effect of dihydrotestosterone on melatonin secretion and the expression of melatonin receptors and apoptosis‐related factors in sheep epididymides

“…The up‐regulation of the Bax/Bcl‐2 ratio and Caspase‐3 expression indicates apoptosis (Simões et al, 2013). DHT plays an anti‐apoptotic role by modulating the AR pathway in anterior pituitary and Sertoli cells of rats (Magri et al, 2016; Simões et al, 2013), granulosa cells of sheep antral follicles (Duan et al, 2021) and U18666A‐induced C6 cells (Bing et al, 2015; Yao et al, 2016). Therefore, we treated sheep epididymal epithelial cells with DHT in vitro and detected the expression of apoptosis‐related factors.…”