Koh Shinoda

Coexistence of the stigmoid body and estrogen receptor in some neuronal groups involved in rat reproductive functions

Recent immunohistochemical studies have suggested that the forebrain distribution of stigmoid bodies, marked by an antibody against placental aromatase-associated antigen X-P2 (PAX), overlaps with that of the common binding sites of androgen and estrogen. In the present light- and electron-microscopy study the coexistence of stigmoid bodies and estrogen receptors (EsR) is immunohistochemically examined and quantitatively analyzed in the medial preoptic region, part of the bed nucleus of the stria terminalis and part of the medial amygdaloid nucleus of young female rats. Light microscopy with double immunostaining for PAX and EsR in all three regions indicates that 75-84% of the total of PAX-immunoreactive stigmoid structures are present in neurons which also contain EsR-immunoreactive nuclei, and that 75-78% of EsR-immunoreactive neurons contain PAX-immunoreactive inclusions. Electron microscopic analysis confirms that 70-80% of stigmoid body-containing neurons have EsR-immunoreactive nuclei. These results indicate that the majority of the stigmoid bodies and EsRs intimately coexist, strongly suggesting a functional interrelationship in brain regions which are involved in rat reproductive functions. Stigmoid bodies may play a role in subneuronal EsR mechanisms associated with aromatization in these sex steroid targets in rat brain.

Sex-Steroid Receptor Mechanism Related to Neuronal Aromatase and the Stigmoid Body

Recent immunohistochemical analyses of rat brains have established the presence of neuronal aromatase and stigmoid body in interfaces of a sex-steroid/brain axis. Aromatase P450-immunoreactive (AROM-I) neurons, which are present only during embryonic Day 16 to postnatal Day 2 (E16-P2), are found in the anterior medial preoptic nucleus, the periventricular preoptic nucleus, and the ventromedial hypothalamic nucleus. The largest AROM-I cell-group localized in the medial preoptico-amygdaloid neuronal arc (mPO-AM) shows a peak during E18-P2 and gradually diminishes after the perinatal days (but still retains the immunoreactivity in adults). In adults, other groups of AROM-I neurons emerge in the lateral septum, the central amygdaloid nucleus, and the bed nucleus of the stria terminalis. Male-predominant sex difference for aromatase expression has been detected at least in the young-to-adult mPO-AM, reflecting sexually distinct endocrine and behavioral responses in the rat reproductive functions. These results suggest the presence of distinct brain-aromatases with different regulatory systems. Neuronal aromatase may modulate development of sexual dimorphism in neonates and activation of reproductive functions in adults. The stigmoid bodies, marked by placental aromatase-associated antigen X-P2 (PAX) antiserum, are also frequent in the sex-steroid targets of rat brains and intimately coexist with estrogen receptors in the mPO-AM of young females. The neuronal inclusion, suspected as a RNA/protein conglomerate, appears to be induced by the decrease of androgen and/or the increase of estrogen, especially as a result of subneuronal aromatic switching into the estrogenous state. The neuronal aromatase and stigmoid body may play important roles in the pre- and post-receptor steps of subneuronal sex-steroids actions for brain sexual differentiation or induction of reproductive functions.