Endocrine Abstracts

Sexual difference of behavior is primarily attributed by structural sexual dimorphism in the nervous system. Recently, we found two sexually dimorphic systems in the central nervous system: 1) newly identified hypothalamic nucleus expressing estrogen receptor (ER) alpha and 2) gastrin releasing peptide (GRP) system in the spinal cord.

Sagittalis nucleus of the hypothalamus (SGN), situated between the arcuate nucleus and ventromedial nucleus, is larger in male than in female. Adult female rats have estrous cycle-related variations in the ER alpha containing cell distribution, decreasing during proestrus phase of the cycle. Treatment of neonatal female with testosterone eliminated sexual difference. SGN has potential as a key component of neuronal circuits, essential for sex steroid-dependent functions and behavior.

Androgen receptor (AR)-expressing neurons in the lumbar segments 3–4 projected their axons containing GRP to lower lumbar spinal cord, innervating autonomic regions that are known to control erection and ejaculation, and spinal nucleus of the bulbocavernosus, which also innervates striated muscles attached to the base of the penis. These target regions expressed the specific receptor for GRP (GRP-R). This system is vestigial in female and in males with genetic dysfunction of androgen receptors. Pharmacological stimulation of GRP-R restored penile reflexes, and antagonistic blockage of GRP-R attenuated these reflexes.

In addition, green fluorescent protein (GFP)-tagged sex steroid receptors were visualized by real-time imaging to reveal specific dynamism of each receptor (AR/ERs). Taken together, molecular imaging techniques with GFP and neuroanatomical approach by using immunohistochemistry offer new avenues for more detailed understanding of sexual behavior.

References: Sakamoto H et al. Nat Neurosci 2008 11 634–636.

Mori H et al. Proc Natl Acad Sci USA 2008 105 13632–13637.

Kaku N et al. Endocrinology 2008 149 3960–3969.