Anterior pituitary cell population control: basal cell turnover and the effects of adrenalectomy and dexamethasone treatment.
We have used an extremely accurate, dedicated, real time computerized image analysis system to facilitate the manual quantification of changes in the prevalence of mitotic figures and apoptotic bodies in male rat pituitary following surgical adrenalectomy and, 14 days later, dexamethasone treatment. Under basal conditions, the prevalence of mitotic figures and apoptotic bodies was 0.066+/-0.016% and 0.030+/-0.012% (mean+/-SE) respectively. Dexamethasone treatment reduced the prevalence of mitotic figures and, in adrenalectomized animals, produced a highly significant and reproducible burst of apoptotic activity that peaked 48 h after the beginning of treatment (0.261+/-0.022%) before falling sharply to control levels within a further 8 h. Two weeks after the start of dexamethasone treatment, total pituitary cell numbers continued to decline. The rate of accumulation of mitotic figures in vivo after colchicine treatment indicates that mitosis is histologically overt in 2 microm thick hematoxylin and eosin stained sections under the light microscope for around 80 min; that apoptosis--identified as classical apoptotic bodies--is overt for 44 min and that, on average, a young, adult, male rat anterior pituitary cell either dies or divides as frequently as once every 60-70 days. These data show that transient and apparently trivial fluctuations in the prevalence of apoptotic and mitotic events have a profound effect on pituitary cell population dynamics, and demonstrate that dexamethasone treatment of adrenalectomized rats produces a decline in total anterior pituitary cell numbers that continues for at least 2 weeks after the start of glucocorticoid treatment.
Nolan
L A
LA
Dorothy Crowfoot Hodgkin Laboratories, Division of Medicine, Bristol Royal Infirmary, UK.
Kavanagh
E
E
Lightman
S L
SL
Levy
A
A
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003199:Computer Systems; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008938:Mitosis / Q000187:drug effects / Q000502:physiology; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone