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

PENNACCHIO GISELA ERIKA; AYALA CAROLINA; SANCHEZ MARIA BELEN; MORENO-SOSA, MARIA TAMARA; CAMPO-VERDE FIORELLA; JAHN GRACIELA ALMA; VALDEZ SUSANA RUTH; SOAJE MARTA; ROSALES JUAN (AGRADECIMIENTOS)

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2022

0028-3835

Abstract Introduction: OFA 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 during late pregnant and lactation. We explored if the expression of MBH components, including various receptors (R) and proteins that regulate the dopaminergic system is altered in mid-lactating OFA compared to SD rats, which may be associated to the abnormality. Methods: Four groups of mid-lactating rats were used: continuous lactation; pups separated overnight; 30 min suckling (S); 2h or 4h S after separation. Mothers were sacrificed to obtain serum for PRL RIA and MBHs to determine tyrosine hydroxylase (TH), PRL33 R, PRL signaling molecules (activator: STAT5b; inhibitors: SOCS1, SOCS3, CIS), opioids (PENK, PDYN)34 and µ- and -opioid R (MOR, KOR) mRNA expression by qPCR and phospho-TH (p-TH) and TH proteins by35 Western blot. Results: suckling-induced PRL was lower in OFA and p-TH expression diminished in both36 strains. Separation increased TH mRNA and protein in SD, which decreased after 4h S, but OFA protein levels37 remained unchanged. Separation of pups also resulted in decreased PRL-R and CIS expression in SD but38 increased PRL-R and SOCS3 in OFA. Despite the lower PRL-R, STAT5b, SOCS1 and SOCS3 levels in OFA39 compared to SD, suckling diminished them further. We observed subtle changes in SD opioids and their R, but40 in OFA, suckling decreased PENK, KOR and MOR. Conclusion: the different patterns of TH, opioids, their R,41 and PRL signaling inhibitors expression with conserved TH activation by suckling may disturb the balance42 between stimulation and inhibition of PRL release resulting in impaired suckling-induced PRL secretion in OFA43 rats.