Abstract / Description of output
Exposure to stress during pregnancy can programme adult hypothalamo-pituitary-adrenal (HPA) axis responses to stress. In rats, prenatal social stress (PNS; 10 min/day on gestational days 16-20) results in exaggerated HPA axis responses to iv interleukin-1 (IL-1) challenge in the adult offspring.
Neurosteroids can reduce HPA responses and we previously found that peripheral administration of 5α-reduced metabolites of testosterone (5-androstan-3,17-diol) or progesterone (allopregnanolone) acutely reverse the hyper-responsive HPA phenotype in male and female PNS offspring, respectively. Here we tested whether PNS rats have deficits in central neurosteroid production by quantifying mRNA expression for neurosteroid-synthesizing enzymes in the nucleus tractus solitarii (NTS) of adult control and PNS male and female rats by in situ hybridisation. PNS did not alter 3α-hydroxysteroid dehydrogenase (3αHSD) mRNA levels in the NTS in either sex, but 5α-reductase (5αR) mRNA levels were reduced in PNS offspring compared with controls. Next, we injected adenoviral vectors (AdV-5αR/3αHSD) to up-regulate 5αR and 3αHSD mRNA expression, or control AdV (AdV-eGFP) into the NTS. Nine days later control and PNS female rats were blood sampled pre- and post IL-1 (500ng/kg iv) challenge. IL-1 increased plasma ACTH levels in control offspring, but responses were greater in PNS/sham (AdV-eGFP) offspring. AdV-5αR/3αHSD treatment increased 5αR and 3αHSD mRNA in the NTS and normalised HPA axis hyper-responses in the PNS rats. Hence, down-regulation of neurosteroid production in the brain underlies HPA axis hyper-responsiveness in prenatally programmed offspring.
Support: BBSRC/CAPES
Neurosteroids can reduce HPA responses and we previously found that peripheral administration of 5α-reduced metabolites of testosterone (5-androstan-3,17-diol) or progesterone (allopregnanolone) acutely reverse the hyper-responsive HPA phenotype in male and female PNS offspring, respectively. Here we tested whether PNS rats have deficits in central neurosteroid production by quantifying mRNA expression for neurosteroid-synthesizing enzymes in the nucleus tractus solitarii (NTS) of adult control and PNS male and female rats by in situ hybridisation. PNS did not alter 3α-hydroxysteroid dehydrogenase (3αHSD) mRNA levels in the NTS in either sex, but 5α-reductase (5αR) mRNA levels were reduced in PNS offspring compared with controls. Next, we injected adenoviral vectors (AdV-5αR/3αHSD) to up-regulate 5αR and 3αHSD mRNA expression, or control AdV (AdV-eGFP) into the NTS. Nine days later control and PNS female rats were blood sampled pre- and post IL-1 (500ng/kg iv) challenge. IL-1 increased plasma ACTH levels in control offspring, but responses were greater in PNS/sham (AdV-eGFP) offspring. AdV-5αR/3αHSD treatment increased 5αR and 3αHSD mRNA in the NTS and normalised HPA axis hyper-responses in the PNS rats. Hence, down-regulation of neurosteroid production in the brain underlies HPA axis hyper-responsiveness in prenatally programmed offspring.
Support: BBSRC/CAPES
Original language | English |
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Publication status | Published - 2011 |
Event | British Society for Neuroendocrinology Annual Meeting 2011 - Cambridge, United Kingdom Duration: 3 Jul 2011 → 5 Jul 2011 |
Conference
Conference | British Society for Neuroendocrinology Annual Meeting 2011 |
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Country/Territory | United Kingdom |
City | Cambridge |
Period | 3/07/11 → 5/07/11 |