Neural tissue‐specific epidermal growth factor (EGF)‐like domain containing protein, NEII2, plays an important role in the central regulation of puberty onset in the female rat hypothalamus

Abstract

In the present study we determined if NELL2, a neural tissue‐specific protein containing 6 epidermal growth factor (EGF)‐like repeat domains, plays an important role in the regulation of puberty initiation in the rat hypothalamus. We originally found that NELL2 is a new estrogen‐responsive gene in hypothalami derived from estrogen‐sterilized and control rats using a PCR differential display. In the 40‐day‐old female rat hypothalamus, NELL2 was up‐regulated by neonatal estrogen treatment. In situ hybridization his to chemistry showed that NELL2 is very abundant in the ventromedial hypothalamic nucleus that is responsible for the control of sex behavior. NELL2 mRNA level in the medial basal hypothalamus showed a dramatic increase before female puberty onset, which suggests that NELL2 may be involved in the process regulating female puberty onset. We attemped to block NELL2 synthesis with intrace rebroventricular injection of an antisense oligodeoxynucleotide (ODN) to the NELL2 mRNA, and examined its effect ...