Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints

Abstract

Vasopressin neurons in the bed nucleus of the stria terminalis and amygdala and vasotocin neurons in homologous areas in non-mammalian vertebrates show some of the most consistently found neural sex differences, with males having more cells and denser projections than females. These projections have been implicated in social and reproductive behaviors but also in autonomic functions. The sex differences in these projections may cause as well as prevent sex differences in these functions. This paper discusses the anatomy, steroid dependency, and sexual differentiation of these neurons. Although the final steps in sexual differentiation of vasopressin/vasotocin expression may be similar across vertebrate species, what triggers differentiation may vary dramatically. For example, during development, estrogen masculinizes vasopressin expression in rats but feminizes its counterpart in Japanese quail. Apparently, nature consistently finds a way of maintaining sex differences in vasopressin and vasotocin pathways, suggesting that the function of these differences is important enough that it was conserved during evolution.

Fig. 1

Sexually dimorphic AVP and vasotocin (AVT) projections in rat and quail brains. (A) Dark-field microphotographs of AVP-ir fiber networks (arrows) in the lateral septum (LS) of a female (left) and male rat (right); * lateral ventricle. (B) Diagram of most prominent AVP-ir projections in rats, modified from De Vries et al. (1985). Steroid-sensitive projections (black lines) run from BST (circles) and MeA (MA, circles) to LS, ventral pallidum (VP), olfactory tubercle (Tu), lateral habenular nucleus (LH), midbrain central gray (CG), dorsal raphe nucleus (DR), locus coeruleus (LC), and ventral hippocampus (Hip). Question marks indicate projections to Hip, mediodorsal nucleus of the thalamus (MD), ventral tegmental area (VT), substantia nigra (SN), which disappeared after castration but not after lesioning the BST. Steroid-insensitive projections (gray lines) originate in SCN (triangles), PVN (squares), and supraoptic nucleus (SON, squares). (C) Bright-field photomicrographs of AVT-ir fiber networks in the lateral septum of male (M) and female Japanese quail (F), treated during development with oil (top panels), estradiol benzoate (EB; middle panels), or the aromatase inhibitor R76 (R76; bottom panels), gonadectomized three weeks post-hatching, and treated with testosterone for another two weeks. Note that AVT fibers are absent in the oil-treated female and EB-treated male and female quail.