A comparison of hypothalamic cell numbers in dwarf and normal weight rats exposed prenatally to methylazoxymethanol (MAM).
Growth deficiencies follow MAM exposure during the period when the growth hormone releasing factor (GRF) cells of the hypothalamus form, while animals exposed slightly later in gestation when the inhibitors of growth hormone release are forming, exhibit giantism. Counts of sample regions of the hypothalamus have shown that rats treated in utero on the 14th day of gestation have reductions in the number of GRF cells, increases in the number of SRIF (somatotropin release inhibiting factor) cells, and alterations of pituitary structure. These effects occurred in all treated subjects, even though obvious effects on body size were present in a small fraction of the treated animals. The present study was designed to examine the effect of 20 mg/kg MAM on the 13th day of gestation (a peak period for production of GRF cells) on GRF and SRIF cell numbers, in a large sample of dwarf-treated rats, normal weight-treated rats, and controls. The results of total counts of hypothalamic cells identified by immunocytochemistry demonstrated significant reductions in GRF cells in both dwarf and normal weight rats exposed to MAM, compared to controls, with no difference between the two treated groups. Like pituitary weights, the neuron counts were significantly correlated with body weight only in dwarf animals. SRIF cell numbers were equivalent to those in controls, suggesting that the increase reported earlier may have been due to a rebound effect in proliferation rather than some response of SRIF cells to GRF cell reduction.(ABSTRACT TRUNCATED AT 250 WORDS)
Rodier
P M
PM
Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, NY 14642.
Kates
B
B
White
A L
AL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D004392:Dwarfism / Q000473:pathology*; D005260:Female; D005865:Gestational Age; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D008938:Mitosis / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D012016:Reference Values; D013004:Somatostatin / Q000032:analysis
D013004:Somatostatin; D008746:Methylazoxymethanol Acetate; D013007:Growth Hormone-Releasing Hormone; C030667:methylazoxymethanol