title: 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 (PRLRlong) 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.
authors.affiliation: Laboratorio de Reproducción y Lactancia, IMBECU, CCT-CONICET Mendoza, Casilla de Correos 855, 5500 Mendoza, Argentina. svaldez@mendoza-conicet.gov.ar
authors.forename: Susana R
authors.initials: SR
authors.lastname: Valdez
authors.forename: Melisa M
authors.initials: MM
authors.lastname: Bonafede
authors.forename: Norma B
authors.initials: NB
authors.lastname: Carreño
authors.forename: Ricardo P
authors.initials: RP
authors.lastname: Deis
authors.forename: Graciela A
authors.initials: GA
authors.lastname: Jahn
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004971:Estrus; D004986:Ether / Q000494:pharmacology; D005260:Female; D007774:Lactation / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D010121:Oxytocin / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004986:Ether; D011374:Progesterone; D004958:Estradiol; D010121:Oxytocin; D011388:Prolactin; D003975:Diazepam; D003345:Corticosterone