Sex differences in urocortin 1 dynamics in the non-preganglionic Edinger-Westphal nucleus of the rat.

Women have higher vulnerability to stress and stress-induced diseases than men. Estrogen may be involved in the control of sex-dependent stress adaptation via estrogen receptors alpha and beta (ERalpha/beta). Urocortin 1 (Ucn1) in the npEW plays an important role in stress adaptation. We hypothesize that the activity of npEW-Ucn1 neurons differs between sexes and is related to estrogen signalling. We here indicate by immunocytochemistry the absence of ERalpha and the presence of ERbeta in the npEW-Ucn1 neurons. Q-RT-PCR of the npEW confirmed this notion, demonstrating that in male rats ERbeta mRNA was almost 5 times higher than in females in di-estrus. Furthermore, Ucn1 mRNA in males was nearly 10 times and 1.6 times higher than in females in di- and pro-estrus, respectively, indicating a sex-dependent difference in Ucn1 biosynthetic activity. Since, at the same time, immunocytochemistry revealed that the amount of Ucn1 peptide stored in the cell bodies of the npEW-Ucn1 neurons did not differ between males and females, as judged on the basis of the number and immunosignal density of these neurons, we propose that the rate of axonal Ucn1 transport and, possibly, the strength of Ucn1 secretion, are dependent on sex to the same degree as is Ucn1 biosynthesis.