NELL2 participates in formation of the sexually dimorphic nucleus of the pre-optic area in rats.
Formation of the sexually dimorphic nucleus of the pre-optic area (SDN-POA) in the rat hypothalamus shows a sexually differential development of neurons. Volume of the SDN-POA in males is much bigger than that in females which is because of a neuroprotective effect of estradiol converted from circulating testosterone during a critical period of brain development. We found that neural epidermal growth factor-like like-2 (NELL2), a neural tissue-enriched protein, is a potential downstream target of estrogen. In this study, we examined a possible role of NELL2 in the development of the SDN-POA and in the normalcy of sexual behavior in the male rats. NELL2 was expressed and co-localized with estrogen receptor alpha in the SDN-POA. A blockade of NELL2 synthesis in the brain during postnatal day 0 (d0) to d4 by an intracerebroventricular injection of an antisense NELL2 oligodeoxynucleotide, resulted in a decrease in volume of the SDN-POA in males. Interestingly, it reduced some components of the male sexual behavior such as mounting and intromission, but not the sexual partner preference in adulthood. In vitro study using the hippocampal neuroprecursor HiB5 cells showed that NELL2 has a protective effect from a cell death condition. These data suggest that a relevant expression of NELL2 in the neonatal brain is important for the estrogen-induced normal development of the SDN-POA and the normalcy of sexual behavior in male rats.
Jeong
Jin Kwon
JK
Department of Biological Sciences, University of Ulsan, Ulsan, South Korea.
Ryu
Byung Jun
BJ
Choi
Jungil
J
Kim
Dong Hee
DH
Choi
Eun Jung
EJ
Park
Jeong Woo
JW
Park
Joong Jean
JJ
Lee
Byung Ju
BJ
D000818:Animals; D002460:Cell Line; D005260:Female; D008297:Male; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011247:Pregnancy; D011301:Preoptic Area / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000502:physiology*
C491252:Nell2 protein, rat; D009419:Nerve Tissue Proteins