The effects of testosterone and oestrogen on gonadectomised and intact male rat anterior pituitary mitotic and apoptotic activity

Abstract

We have used a direct, non-immunochemical and highly accurate method to quantify the effects of testosterone and oestrogen on mitotic and apoptotic activity in the young, male rat anterior pituitary in vivo. Surgical gonadectomy resulted in a 3-fold increase in mitotic activity by the fourth post-operative day, which returned gradually to levels seen in intact animals over the subsequent 3-4 weeks. Both a single dose of Sustanon, a mixture of long-acting testosterone esters in arachis oil, and the same dose divided over 7 days (starting 6 days after gonadectomy), initially suppressed mitotic activity to levels seen in intact animals, but was associated after 48-96 h with a wave of increased mitotic activity. The latter was blocked by co-administration of Sustanon with the non-steroidal aromatase inhibitor letrozole and was not seen when the non-aromatisable androgen dihydrotestosterone was substituted for Sustanon. Oestrogen alone in gonadectomised and intact rats produced a marked increase in mitosis as expected. With the exception of a transient increase in response to a single high-dose injection of Sustanon in gonadectomised animals, apoptotic activity was unaffected by all of the above. This study suggests that pituitary mitotic activity is tonically inhibited by gonadal hormone production (at least in the short term) in adult male rats. The study also suggests that supraphysiological testosterone treatment -while unable to reduce anterior pituitary mitotic activity in untreated, intact animalssuppresses the early increase in mitotic activity induced by gonadectomy. Oestrogen, either exogenous or generated locally by aromatisation, stimulates anterior pituitary mitotic activity in a time-dependent manner.

Estradiol Increases the Bax/Bcl-2 Ratio and Induces Apoptosis in the Anterior Pituitary Gland

“…The activation of cell proliferation necessarily primes the cellular apoptotic program that, unless abrogated by appropriate survival signals, removes the affected cell [37]. It has been reported that dexamethasone or testosterone treatments after adrenalectomy or gonadectomy induce mitotic and apoptotic activity in the anterior pituitary [38,39]. Our results suggest that chronic estrogen treatment may trigger both proliferation and apoptosis of anterior pituitary cells, processes closely linked to each other.…”

Aromatase enzyme expression in acromegaly and its possible relationship with disease prognosis

“…Testosterone has been shown to increase mitotic activity in pituitary glands of rats and to increase PRL levels in men [12,22]. Deterioration of visual field defects and increased tumor size has been reported in men with macroprolactinoma receiving testosterone replacement therapy [23].…”

“…Estrogens generated locally by aromatization may be involved in the activation of anterior pituitary mitotic activity [13,27]. Therefore, increased aromatase expression may lead to the growth of pituitary tumors.…”

Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia

“…The treatment group received letrozole orally (Femara, Novartis group, 1 mg/kg per day dissolved in 10% gelatin; Nolan & Levy 2006). The gelatin preparation was consumed avidly by the rats.…”