Androgen enhances neuronal degeneration in the developing preoptic area: apoptosis in the anteroventral periventricular nucleus (AVPvN-POA).
Perinatal treatment of female rats with androgen decreases the nuclear volume of the anteroventral periventricular nucleus of the preoptic area (AVPvN-POA). In order to examine the effect of androgen on neurogenesis, bromodeoxyuridine (BrdU) was given once on Day 15 of gestation (= E15) to pregnant rats that also received testosterone propionate (TP) injections. When examined at E17, the number of BrdU-labeled neurons in the AVPvN-POA was not significantly different among control female, male, and androgenized female fetuses, suggesting that androgen does not interfere with neurogenesis. At E21, a significant reduction of BrdU-labeled AVPvN neurons was observed in males and androgenized females. These findings support the hypothesis that elimination of a population by cell death is enhanced in males and androgenized females. Similar selective elimination of the AVPvN neurons occurred in the female following neonatal TP treatment. In order to investigate the nature of androgen-induced cell death in the AVPvN-POA, specific labeling of nuclear DNA fragmentation was performed by the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method. The number of TUNEL-positive cells was significantly greater in neonatally androgenized females, compared to that in control females. Since DNA fragmentation is considered the most characteristic feature of apoptosis, and TUNEL method is based on direct, specific labeling of DNA fragmentation in nuclei in situ, the neuronal death in the AVPvN-POA is apoptotic, and perinatal androgen may induce the selective apoptotic cell death in the AVPvN-POA.
Arai
Y
Y
Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan.
Murakami
S
S
Nishizuka
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005865:Gestational Age; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011301:Preoptic Area / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012733:Sex Differentiation / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology*
D013739:Testosterone