Submitted on April 12, 2006
Accepted on June 23, 2006
Prolactin and the expression of suppressor of cytokine signaling-3 (SOCS-3) in the sheep adrenal before birth
Sheridan Gentili1, Jeff S. Schwartz2, Michael J. Waters3, and I Caroline McMillen1*
1 Discipline of Physiology, Centre for the Early Origins of Adult Health, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia; Sansom Institute, Research Centre for the Early Origins of Adult Health, School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia, Australia
2 Discipline of Physiology, Centre for the Early Origins of Adult Health, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia
3 Institute for Molecular Bioscience and School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
* To whom correspondence should be addressed. E-mail: caroline.mcmillen{at}unisa.edu.au.
The fetal pituitary-adrenal axis plays a key role in the fetal response to intrauterine stress and in the timing of parturition. The fetal sheep adrenal is relatively refractory to stimulation in mid gestation before the prepartum activation at ~135d gestation (term=147±3d). The mechanisms underlying the switch from adrenal quiescence to activation are unclear. We have investigated the expression of SOCS-3, a putative inhibitor of tissue growth, in the fetal sheep adrenal between 50-145d gestation and in the adrenal of the growth restricted fetal sheep in late gestation. SOCS-3 is activated by a range of cytokines including prolactin (PRL) and we have determined whether PRL administered in vivo or in vitro stimulates SOCS-3 mRNA expression in the fetal adrenal in late gestation. There was a decrease (P<0.005) in SOCS-3 expression in the fetal adrenal between 54-133d and 141-141d gestation. PRL administration significantly increased adrenal SOCS-3 mRNA expression (P<0.05). Similarly, there was an increase (P<0.05) in SOCS-3 mRNA expression in adrenocortical cells in vitro after exposure to PRL (50ng/ml). Placental restriction had no effect on SOCS-3 expression in the adrenal during late gestation. In summary, the decrease in the expression of the inhibitor SOCS-3 after 133d gestation may be permissive for a subsequent increase in fetal adrenal growth before birth. We conclude that factors other than PRL act to maintain adrenal SOCS-3 mRNA expression before 133d gestation but that acute elevations of PRL can act to upregulate adrenal SOCS-3 expression in the sheep fetus during late gestation.
