Alterations in hypothalamic mechanisms associated with reduced suckling-induced PRL secretion in the lactation deficient OFA hr/hr rat.

PENNACCHIO GE; AYALA C; SANCHEZ MB; MORENO-SOSA MT; CAMPO VERDE ARBOCCO F; JAHN GA; VALDEZ SR; SOAJE M

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2023 vol. 113 p. 304 - 318

0028-3835

IntroductionOFA hr/hr rats have deficient lactation with impaired suckling-induced PRL release. Unlike their background strain,Sprague-Dawley (SD) rats, OFA rats display abnormal mediobasal hypothalamus (MBH) dopaminergic tone duringlate pregnantcy and lactation. We explored if the expression of MBH components, including various receptors (Rs) andproteins that regulate the dopaminergic system, is altered in mid-lactating OFA compared to SD rats, which may beassociated with the abnormality.MethodsFour groups of mid-lactating rats were used: continuous lactation; pups separated overnight; 30-min suckling (S); and 2h or 4 h S after separation. Mothers were sacrificed to obtain serum for PRL RIA and MBHs to determine tyrosinehydroxylase (TH), PRL-R, PRL signaling molecules (activator: STAT5b; inhibitors: SOCS1, SOCS3, CIS), opioids(PENK, PDYN), and μ- and κ-opioid R (MOR, KOR) mRNA expression by qPCR and phospho-TH (p-TH) and THproteins by Western blot.ResultsSuckling-induced PRL was lower in OFA and p-TH expression diminished in both strains. Separation increased THmRNA and protein in SD, which decreased after 4 h S, but OFA protein levels remained unchanged. Separation ofpups also resulted in decreased PRL-R and CIS expression in SD but increased PRL-R and SOCS3 in OFA. Despitethe lower PRL-R, STAT5b, SOCS1, and SOCS3 levels in OFA compared to SD, suckling diminished them further.We observed subtle changes in SD opioids and their R, but in OFA, suckling decreased PENK, KOR, and MOR.ConclusionThe different patterns of TH, opioids, their R, and PRL signaling inhibitor expression with conserved TH activation bysuckling may disturb the balance between stimulation and inhibition of PRL release resulting in impaired sucklinginducedPRL secretion in OFA rats.