Respiratory regulation by steroids in newborn rats: a sex-specific balance between allopregnanolone and progesterone receptors

Abstract

We tested the hypothesis that the effects of progesterone on apnoea frequency in newborn rats are the result of a balance between its neuroactive metabolite allopregnanolone (GABAa receptor modulator) and progesterone receptors. We used male and female rats between 10 and 12 days of age and recorded respiratory and metabolic parameters (whole-body plethysmography), and assessed the frequency and duration of apnoeas under normoxia. We tested the effects of a single injection of progesterone (4 mg kg⁻¹, i.p.), finasteride (10 mg kg⁻¹, i.p. – 5α-reductase antagonist: blocks the conversion of progesterone to allopregnanolone), finasteride+progesterone, or agonists of the nuclear or membrane progesterone receptors (R5020 or Org-od-02-0, 4 mg kg⁻¹). To test the hypothesis that chronic exposure to progesterone reduces the frequency of apnoeas we used male and female daily treated with progesterone between postnatal days 3–12. The acute injection of progesterone reduced minute ventilation and metabolic rate and increased the frequency of apnoeas. Finasteride decreased the frequency of apnoeas, and finasteride+progesterone did not increase apnoea frequency but decreased minute ventilation in female rats. While R5020 decreased apnoea frequency only in males, Org-od-02-0 decreased apnoea frequency in males and females and decreased respiratory frequency in females. Chronic progesterone treatment reduced apnoea frequency more efficiently in males than in females, but in females (not in males) an acute injection of caffeine (the gold standard for the treatment of apnoea in preterm neonates) further reduced apnoea frequency. Apnoea frequency in newborn rats is in part determined by a sex-specific balance between allopregnanolone, GABAa receptors, and progesterone receptors.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://ift.tt/2zfrHLC
via IFTTT