Vk. Patchev et al., IMPLICATIONS OF ESTROGEN-DEPENDENT BRAIN ORGANIZATION FOR GENDER DIFFERENCES IN HYPOTHALAMO-PITUITARY-ADRENAL REGULATION, The FASEB journal, 9(5), 1995, pp. 419-423
Estrogens, derived from the aromatization of testosterone in the brain
, account for sex-specific organization of neural circuits controlling
gonadotropin release and sexual behavior. This study examines the pos
sible organizing role of perinatal gonadal steroids in the manifestati
on of known, albeit unexplained, male-female differences in basal and
stress-related adrenocortical secretion. We document here the existenc
e of gender-specific differences in the gene expression of hypothalami
c corticotropin-releasing hormone (CRH), and hippocampal and hypothala
mic glucocorticoid receptors (GR), diurnal corticosterone secretion, a
s well as in the responsiveness of CRH and GR mRNA levels to exogenous
estradiol, In addition, we report that neonatal estrogenization of fe
male rats profoundly affects several regulatory substrates of the hypo
thalamo-pituitary-adrenal (HPA) axis, namely, the gene expression of C
RH, arginine-vasopressin (AVP) and GR in the brain, and the responsive
ness of these parameters to estrogen, The neonatal treatment appeared
to ''defeminize'' a number of neuroendocrine mechanisms related to HPA
function; these changes were reminiscent of those observed in earlier
studies on sexual differentiation of reproductive behavior and hormon
al secretion, The results indicate a pivotal role for estrogens during
early development for the determination of gender-specific difference
s in HPA function in the mature animal and demonstrate for the first t
ime that the brain-organizing actions of gonadal steroids may extend t
o nonreproductive neuroendocrine axes.