Laboratorio de Reproducción y Lactancia, IMBECU-CONICET, Casilla de Correo 855, Mendoza, Argentina.
FCEN-Universidad Nacional de Cuyo, Mendoza, Argentina.
Neuroendocrinology. 2023;113(3):304-318. doi: 10.1159/000526751. Epub 2022 Aug 26.
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 pregnancy 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 with the abnormality.
Four groups of mid-lactating rats were used: continuous lactation; pups separated overnight; 30-min suckling (S); and 2 h or 4 h S after separation. Mothers were sacrificed to obtain serum for PRL RIA and MBHs to determine tyrosine hydroxylase (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 TH proteins by Western blot.
Suckling-induced PRL was lower in OFA and p-TH expression diminished in both strains. Separation increased TH mRNA and protein in SD, which decreased after 4 h S, but OFA protein levels remained unchanged. Separation of pups also resulted in decreased PRL-R and CIS expression in SD but increased PRL-R and SOCS3 in OFA. Despite the 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.
The different patterns of TH, opioids, their R, and PRL signaling inhibitor expression with conserved TH activation by suckling may disturb the balance between stimulation and inhibition of PRL release resulting in impaired suckling-induced PRL secretion in OFA rats.
OFA hr/hr 大鼠的泌乳功能不足，吮吸诱导的 PRL 释放受损。与它们的背景品系 Sprague-Dawley（SD）大鼠不同，OFA 大鼠在妊娠晚期和哺乳期表现出中脑基底核（MBH）多巴胺能张力异常。我们探讨了中哺乳期 OFA 大鼠与 SD 大鼠相比，MBH 成分的表达是否发生改变，包括各种受体（R）和调节多巴胺能系统的蛋白质，这可能与异常有关。
使用了四组中哺乳期大鼠：连续泌乳；幼崽分离过夜；30 分钟吮吸（S）；分离后 2 小时或 4 小时 S。母亲被处死以获得血清进行 PRL RIA 和 MBH 以确定酪氨酸羟化酶（TH）、PRL-R、PRL 信号分子（激活剂：STAT5b；抑制剂：SOCS1、SOCS3、CIS）、阿片类物质（PENK、PDYN）和 µ-和 κ-阿片类 R（MOR、KOR）mRNA 的表达，通过 qPCR 和磷酸化 TH（p-TH）和 TH 蛋白通过 Western blot 确定。
OFA 大鼠的吮吸诱导 PRL 较低，两种品系的 p-TH 表达均减少。分离增加了 SD 中的 TH mRNA 和蛋白，4 小时 S 后减少，但 OFA 蛋白水平保持不变。幼崽分离也导致 SD 中的 PRL-R 和 CIS 表达减少，但 OFA 中的 PRL-R 和 SOCS3 增加。尽管 OFA 大鼠的 PRL-R、STAT5b、SOCS1 和 SOCS3 水平低于 SD 大鼠，但吮吸进一步降低了它们的水平。我们观察到 SD 阿片类物质及其 R 的细微变化，但在 OFA 中，吮吸减少了 PENK、KOR 和 MOR。
与吮吸引起的 TH 激活一致，TH、阿片类物质、它们的 R 和 PRL 信号抑制剂表达的不同模式可能会扰乱刺激和抑制 PRL 释放之间的平衡，导致 OFA 大鼠吮吸诱导的 PRL 分泌受损。
