Modulation of cardiac oxytocin receptor and estrogen receptor alpha mRNAs expression following neonatal oxytocin treatment.

Oxytocin (OT) is known for its role in reproduction. However, evidence has emerged suggesting its involvement in the regulation of the cardiovascular system. Here we examine the hypothesis that neonatal exposure to OT can have both short-term and long-lasting consequences on gene expression in heart tissue. On the first day of postnatal life, female and male prairie voles (Microtus ochrogaster) were randomly assigned to receive one of following treatments: 50 microl i.p. injection of (a) 3 microg OT (b) 0.3 microg of OT antagonist (OTA), or (c) isotonic saline (SAL). Hearts were collected on postnatal day 1 (D1, 2 h after injection), day 8 (D8), or day 21 (D21), and the mRNA expression for OT receptor (OTR), estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta as a function of age, treatment, and sex were measured using RT-PCR. Neonatal treatment with OT showed a marked increase in cardiac OTR mRNA expression on postnatal D1, but not D8 or D21, in both female and male animals. ERalpha increased as a function of OT treatment only in females. Although significant treatment effects were no longer detected in D8 or D21 animals, there were significant changes in the relative expression of all types of mRNA between D1 and D21 with age-related declines in OTR and ERbeta and increases in ERalpha Neonatal treatment with OTA showed no changes in cardiac OTR, ERalpha, or ERbeta mRNAs expression. The results indicate that during the early postnatal period OT can have rapid effects on the expression of OTR and ERalpha mRNAs and that these effects are mitigated by D8 or D21. Also, with the exception of ERalpha mRNA, the effects are the same in both sexes.

Neonatal oxytocin treatment modulates oxytocin receptor, atrial natriuretic peptide, nitric oxide synthase and estrogen receptor mRNAs expression in rat heart.

Oxytocin (OT) has been implicated in reproductive functions, induction of maternal behavior as well as endocrine and neuroendocrine regulation of the cardiovascular system. Here we demonstrate that neonatal manipulation of OT can modulate the mRNAs expression for OT receptor (OTR), atrial natriuretic peptide (ANP), endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha (ERalpha) in the heart. On the first day of postnatal life, female and male rats were randomly assigned to receive one of the following treatments: (a) 50microl i.p. injection of 7microg OT; (b) 0.7microg of OT antagonist (OTA); or (c) isotonic saline (SAL). Hearts were collected either on postnatal day 1 or day 21 (D1 or D21) and the mRNAs expression of OTR, ANP, inducible NOS (iNOS), eNOS, ERalpha and estrogen receptor beta (ERbeta) were compared by age, treatment, and sex utilizing real time PCR. OT treatment significantly increased heart OTR, ANP and eNOS mRNAs expression on D1 in both males and females, ERalpha increased only in females. While there were significant changes in the relative expression of all types of mRNA between D1 and D21, there were no significant treatment effects observed in D21 animals. OTA treatment significantly decreased basal ANP and eNOS mRNAs expression on D1 in both sexes. The results indicate that during the early postnatal period OT can have an immediate effect on the expression OTR, ANP, eNOS, and ERalpha mRNAs and that these effects are mitigated by D21. Also with the exception of ERalpha mRNA, the effects are the same in both sexes.

Oxytocin selectively increases ERalpha mRNA in the neonatal hypothalamus and hippocampus of female prairie voles.

During neonatal development exogenous oxytocin increases ERalpha immunoreactivity in the hypothalamus of female prairie voles. The purpose of this study was to determine if the increase in ERalpha is associated with an increase in ERalpha mRNA expression and to determine if the effect is specific to ER subtype or if oxytocin also influences ERbeta mRNA expression. On the day of birth female prairie vole pups were treated with oxytocin, an oxytocin antagonist, or saline. Brains were collected and RT-PCR was used to determine the effect of treatment on ER mRNA production in the hypothalamus, hippocampus, and cortex. Within 2h of treatment oxytocin significantly increased ERalpha mRNA expression in the hypothalamus and hippocampus, but not the cortex, while inhibiting the effects of endogenous oxytocin reduced the expression of ERalpha mRNA in the hippocampus. Neonatal treatment did not affect the expression of ERbetamRNA. The results demonstrate that the effects of oxytocin treatment are region and ER subtype specific and that during the neonatal period oxytocin can affect the expression of ERalpha by altering message production. The regional specific changes in ERalpha mRNA expression in females are consistent with studies examining the behavioral and physiological effects of neonatal manipulation of oxytocin in females.