A recently identified hypothalamic nucleus expressing estrogen receptor α

Abstract

We report evidence for the existence of a unique nucleus in the rat hypothalamus. This nerve cell group is situated in the interstitial area between the arcuate nucleus and ventromedial nucleus of the hypothalamus, and is primarily oriented sagittally, in a spindle shape. This nucleus was a well defined structure in Nissl-stained sections because of its location in an otherwise cell-poor zone. This sagittalis nucleus of the hypothalamus (SGN) exhibits significant sex differences in its volume and cell numbers, as defined by Nissl staining and estrogen receptor (ER) ␣ immunoreactivity (ir), being significantly larger in males than in females. Treatment of neonatal females with testosterone eliminated these sex differences. It is noteworthy that adult female rats have estrous cycle-related variations in the ER␣-ir cell distribution, decreasing during the proestrus phase of the cycle. Pharmacological experiments demonstrated that the single injection of estradiol benzoate had a significant effect on the ER␣-ir cell count, suggesting the hormonal responsiveness of SGN neurons. This unique hypothalamic nucleus with its morphological sex differences and hormonal responsiveness is embedded in a region important for the regulation of endocrine functions and sexual behaviors.sexual difference ͉ estrous cycle ͉ calbindinD-28k ͉ sagittalis nucleus A fter the comprehensive neuroanatomical charting of neurons expressing mRNAs for estrogen receptors (1) and subsequent estradiol binding (2), it was assumed that the understanding of the neuroanatomy of estrogen action in the brain was fairly complete. Here, however, we have discerned a hitherto unrecognized cell group that expresses estrogen receptor (ER) ␣ and exhibits sex differences.A number of important sex differences have already been described in the mammalian brain (3, 4). Most of these are organized by the action of the gonadal steroids in the critical period: during the few days before to after birth in rodents (4). In this period, an elevated amount of testosterone (T) is secreted from the male fetal testes and converted to estradiol (E) by the enzyme aromatase in the hypothalamus. Formation of E causes permanent masculinization of the brain (5). This masculinization is also experimentally induced in females by the administration of E in the critical period (3, 6). These morphological sex differences in the brain are likely among the neuroanatomical mechanisms for the physiological sex differences in adult brain function (7,8).At the age of puberty, the functional sex-related differences begin to appear, indicated by a sudden rise in the secretion of gonadotrophic hormones: luteinizing hormone (LH) and follicle-stimulating hormone, followed by an increase in gonadal steroids (9). The gonadal steroids, particularly E, orchestrate the neuroendocrine circuits that coordinate sex-specific behaviors. This E signaling is importantly mediated by ERs (3), which are in fact abundant in the sexual dimorphic nuclei in the hypothalamus, such as the anteroventral periventricular ...

Sagittalis Nucleus: A Novel Hypothalamic Nucleus

“…These neonatal sex steroids also affect the morphology of the SGN because treatment of newborn (P0) female rats with 200 μg of testosterone propionate resulted in a larger SGN (i.e. the female SGN becomes more masculinised) (6).…”

“…The SGN exhibits physiological sex differences in the expression levels of ERα (6). The SGN in males contained more ERα‐ir neurones than that of females, with approximately 2.3‐fold more being present in males (Fig.…”

“…These findings suggest that the sex difference and oestrous cycle‐related variation in ERα‐ir in the SGN are derived from different levels of circulating steroids in each sex and across the oestrous cycle. To investigate whether one of the ovarian steroids, oestradiol, directly regulates the ERα‐ir in the SGN, we administered oestradiol replacement to adult females after ovariectomy (6). ERα‐ir cell numbers in the SGN were significantly elevated after ovariectomy and sharply decreased after oestradiol replacement.…”

“…From these results, we hypothesise that oestrogen negatively regulates the ERα expression in SGN neurones, indicating that the physiological sex differences in ERα‐ir in the SGN are the result of the difference in circulating oestrogen levels between the sexes. In addition, oestrous cycle‐related variations in ERα‐ir cell numbers in cyclic female SGN are also derived from different circulating oestrogen levels at different stages of the oestrous cycle (6).…”

“…When observing oestrogen receptor (ER)α immunoreactivity (‐ir) in sequential sections, a densely packed cluster was noted. After applying traditional Nissl staining followed by immunohistochemical characterisation, we realised that this neural group was a discrete structure that had not been reported previously (6).…”