An aromatase‐associated cytoplasmic inclusion, the “stigmoid body”, in the rat brain: I. Distribution in the forebrain

Abstract

An aromatase-containing neural system was examined in the rat forebrain, using a polyclonal antibody against aromatase-associated human placental antigen X-P2 (hPAX-P2). Numerous dot-like structures, which we have called stigmoid bodies, were immunostained in the preoptico-hypothalamic region, the bed nucleus of the stria terminalis, the medial amygdala, the arcuate nucleus, the subfornical organ, and the area extending from the hypothalamic area to the central gray through the medial forebrain bundle and the periventricular fiber system of the posterior diencephalon. The stigmoid bodies were always found as inclusions in the neuronal cytoplasm. Their diameter was usually 1-3 microns, but exceptionally large forms, over 3 microns, were found in some brain regions, including the area extending from the median preoptic nucleus surrounding the organosum vasculosum laminae terminalis to the anterior medial preoptic nucleus, the periventricular nucleus of the preoptic area, and some parts of the medial preoptic nucleus. Most of these nuclei show sexual dimorphism. The distribution pattern of the hPAX-P2 immunoreactive stigmoid bodies agreed well with that of aromatase activity previously reported in many biochemical studies. Brain regions where the stigmoid bodies were prominent largely coincide with steroid binding locations common to both androgen and estrogen, or regions where both sex steroid receptors are present. Although it still remains to be determined whether aromatase is localized within these stigmoid bodies, it appears likely that they are closely associated with the function of sex steroids at their target sites in the brain.

DYRK1A regulates Hap1–Dcaf7/WDR68 binding with implication for delayed growth in Down syndrome

“…The highest P/S ratio of Hap1 was seen in the hypothalamus (Fig. 1B), in agreement with the finding that SBs are more abundant in the hypothalamus than in other tissues (5,10,14). Thus, these results showed that the use of a detergent-based strategy to enrich SBs in mouse brain was feasible.…”

“…For example, Hap1 is abundantly expressed in the hypothalamus, and its expression in the hypothalamus influences the central control of feeding (9); as a direct result, mice lacking Hap1 are malnourished and die in the early postnatal period (5, 10, 11). The function of Hap1 is also age dependent and appears to be important for postnatal neurogenesis in the paraventricular nuclei, the lateral hypothalamus (5, 11), and the dentate gyrus of the hippocampus (7).The specific function of Hap1 in the hypothalamus may be associated with unique cytoplasmic structures called "stigmoid bodies" (SBs), which are formed by Hap1 in the hypothalamus (12, 13) and appear to be non-membrane-bound, ovoid to circular in shape, and 0.5-3 μm in diameter (14,15). Widely regarded as a determinant marker for SBs, Hap1 is capable of sequestering several important disease-related proteins into SB-like inclusions in cell cultures, including Abelson helper integration site 1 (Ahi1), androgen receptor, TBP, and ataxin-3 (6, 16-18).…”

“…The specific function of Hap1 in the hypothalamus may be associated with unique cytoplasmic structures called "stigmoid bodies" (SBs), which are formed by Hap1 in the hypothalamus (12, 13) and appear to be non-membrane-bound, ovoid to circular in shape, and 0.5-3 μm in diameter (14,15). Widely regarded as a determinant marker for SBs, Hap1 is capable of sequestering several important disease-related proteins into SB-like inclusions in cell cultures, including Abelson helper integration site 1 (Ahi1), androgen receptor, TBP, and ataxin-3 (6, 16-18).…”

Huntingtin associated protein 1 and its functions

“…25 forebrain regions of the rat. 98 Although the subcellular functions of SBs have not yet been understood, it is important to know that SBs contain HAP1. 11,15 SBs containing HAP1 also are found to contain the unknown human placental antigen complex X-P2 (hPAX-P2) and apolipoprotein E receptor, SorLA/LR11 and sortilin (two members of the vacuolar protein sorting 10 (VPS10) domaincontaining family).…”

Brain Aromatization and Its Associated Structures.

“…One is the "necklace olfactory system" immunohistochemically discovered by the PAX antibody [121], and the other is an intriguing neuronal inclusion, the "stigmoid body" , which was also marked by PAX antibody and found specifically in rat preopticohypothalamus and limbic regions involved in reproductive functions [237]. The former is the only distinct unit morphologically identified in the rat primary olfactory system and it has been considered to be involved in "pheromone-induced" olfactory function associated with rat suckling behavior.…”