5α‐reductase mRNA is increased in the rostral ventrolateral medulla (RVLM) of term pregnant rats

Abstract

In term pregnant rats, baseline GABAergic inhibition of the RVLM is increased, while baseline GABAergic inhibition of the hypothalamic paraventricular nucleus (PVN) is decreased. The major metabolite of progesterone, 3α‐hydroxy‐dihydroprogesterone (3α‐OH‐DHP), is a potent endogenous positive modulator of GABAA receptors and CNS levels of this neurosteroid are increased in pregnancy. Local regulation of the enzymes responsible for formation of 3α‐OH‐DHP, 5α‐reductase (5α‐RDA) and 3α‐hydroxysteroid dehydrogenase (3α‐HSD), is one factor which determines brain region specific actions of 3α‐OH‐DHP. Expression of mRNA for 5α‐RDA and 3α‐HSD (reference gene = MAPK) was determined in tissue punches of the RVLM and PVN from nonpregnant (NP) and term pregnant (P) rats. In the PVN, pregnancy did not change relative expression of 5α‐RDA [NP(7)= 1.0 ±0.23; P(7)= 0.64± 0.15] or 3α‐HSD [NP(5)= 1.0 ±0.38; P(6)= 0.84± 0.23]. In the RVLM, expression of 3α‐HSD [NP(5)= 1.0 ±0.54; P(6)= 0.67± 0.44] was not different between NP and P rats. However, there was a strong trend for increased expression of 5α‐RDA in P (5) [2.44± 0.89] compared to NP(5) [1.0 ±0.28] rats. Although preliminary, these data suggest that increased expression of 5α‐RDA in the RVLM of pregnant rats, could result in increased formation of the major metabolite of progesterone and potential positive modulation of GABAA receptors. (NIH HL 36245)