Sexual dimorphism of apoptosis in lactotrophs induced by bromocryptine.
Interruption of lactation provokes a massive degeneration of surplus lactotrophs in the rat pituitary gland. This process was determined to be non-apoptotic in nature, and this observation raised many questions as cell death by apoptosis has been described in several tissues after withdrawal of trophic hormones. In this study we explored various experimental conditions and gathered new information leading to a comprehensive interpretation of the factors involved in the induction of apoptosis in lactotrophs. With this aim, we investigated the apoptogenic role of bromocryptine on lactotrophs in several experimental models involving male and female rats. Even though bromocryptine increased the expression of P53 in all experimental models, apoptosis was only triggered in male and ovariectomised females. In both conditions the oestrogen stimulation is low or nil, and the occurrence of apoptosis can be correlated with the appearance of atypical lactotrophs and the level of P53 expression. The existence of apoptosis was validated with the observation of DNA laddering in electrophoresis. By contrast, in intact females the majority of lactotrophs present signs of an increased prolactin secretion and no DNA fragmentation was found. Endogenous oestrogens probably prevent the deep inhibitory effect of a dopamine agonist and thus block apoptosis. Besides, the morphological analysis of regressing pituitary revealed the coexistence of lactotrophs to be an important factor responsible for tissue remodelling in functional pituitary glands undergoing apoptotic and non-apoptotic cell deaths. The non-apoptotic cell death appeared to be an important factor responsible for tissue remodelling in functional pituitary glands. The present results suggest that the occurrence of apoptosis in regressing lactotrophs caused by bromocryptine is sexually dimorphic and probably associated with the survival effect of endogenous oestrogens in intact females.
Aoki
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MP
Centre of Electron Microscopy, Faculty of Medical Sciences, National University of Córdoba, Casilla Postal 362, X5000EPP Córdoba, Argentina.
Aoki
A
A
Maldonado
C A
CA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008854:Microscopy, Electron; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D011388:Prolactin / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D006727:Hormone Antagonists; D016159:Tumor Suppressor Protein p53; D001971:Bromocriptine; D011388:Prolactin