Lactation deficit in OFA hr/hr rats may be caused by differential sensitivity to stress compared with Wistar and Sprague Dawley rats

Abstract

OFA hr/hr (OFA) rats present a major lactation deficit that impairs offspring survival. To explore whether abnormal stress responsiveness causes this deficit, we compared their hormonal (prolactin, progesterone, and corticosterone) responses to stress (room change and 2-min ether exposure) with those of Wistar and Sprague Dawley (SD) rats. We tested responses during the estrous cycle, pregnancy, lactation, after ovariectomy, and ovarian steroid hormone priming, and responses to suckling. We evaluated hypothalamic expression of receptors for prolactin (PRLR_long) and the isoforms of receptors for progesterone (PRA and B) and estrogen (ERα and β) in late pregnancy. We tested whether administration of an anxiolytic (diazepam) improved lactation. Ether exposure increased circulating levels of the three hormones in the three strains of rats, cycling and ovariectomized, but was less effective in pregnancy and lactation. Elevated estrogen level (estrus and estradiol-treated ovariectomized rats) potentiated the prolactin response more in SD and OFA rats than in Wistar rats. Elevated progesterone level (late pregnancy, lactation, progesterone-treated ovariectomized rats) inhibited the prolactin response less in OFA than in SD or Wistar rats. Ether exposure inhibited the prolactin and oxytocin responses to suckling only in OFA rats. Diazepam treatment increased pup survival rate and the prolactin response to suckling. Hypothalamic total PR mRNA content, assayed by RT-PCR, was higher in pregnant OFA rats compared with SD and Wistar rats, but the PRB/PRA protein ratio determined by Western blot was lowest in Wistar rats, intermediate in OFA rats, and highest in SD rats. The heightened sensitivity to stress of lactating OFA rats may contribute to their lactational deficit and be caused by a combination of hypoprolactinemia and reduced inhibitory capacity of progesterone.

Keywords::

• Corticosterone
• lactation
• prolactin
• ovarian hormones
• pregnancy
• stress

Acknowledgements

The authors are grateful to Dr N. Hagino for oxytocin antibody and to Dr Marta Soaje for critical reading of this article. This paper is dedicated to the memory of Dr Ricardo P. Deis, deceased on 26 April 2008, who was a pioneer in lactation physiology and whose mentorship, counsel, and suggestions greatly enriched this work.

Declaration of interest: This work has been supported by grants PIP 5795/05 and 2298/09 from CONICET (Consejo nacional de investigaciones científicas y técnicas, Argentina) and PICT-R 32529 from the Agencia de Promoción Científica y Tecnológica, Argentina. GAJ and SRV are Career Scientists from CONICET, and MMB has a fellowship from CONICET. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.