Departamento de Fisiologia e Biofísica, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus Soane Nazare de Andrade, Ilheus, Brazil.
Endocrinology. 2020 Apr 1;161(4). doi: 10.1210/endocr/bqaa022.
Hyperprolactinemia causes infertility by suppressing gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion. Because effects of prolactin (PRL) on the hypothalamus usually require estradiol (E2), we investigated the role of E2 in PRL-induced suppression of LH pulses. Ovariectomized (OVX) rats treated with oil or E2 (OVX + E2) received a subcutaneous injection of ovine PRL (oPRL) 30 minutes before serial measurement of LH in the tail blood by enzyme-linked immunosorbent assay. E2 reduced pulsatile LH secretion. oPRL at 1.5 mg/kg further reduced LH pulse frequency in OVX + E2 but had no effect in OVX rats. The higher dose of 6-mg/kg oPRL decreased LH pulse frequency in both OVX and OVX + E2 rats, whereas pulse amplitude and mean LH levels were lowered only in OVX + E2 rats. Kisspeptin immunoreactivity and Kiss1 messenger ribonucleic acid (mRNA) levels were decreased in the arcuate nucleus (ARC) of OVX + E2 rats. oPRL decreased both kisspeptin peptide and gene expression in the ARC of OVX rats but did not alter the already low levels in OVX + E2 rats. In the anteroventral periventricular nucleus, oPRL did not change kisspeptin immunoreactivity and, paradoxically, increased Kiss1 mRNA only in OVX + E2 rats. Moreover, oPRL effectively reduced Gnrh expression regardless of E2 treatment. In this study we used tail-tip blood sampling to determine the acute effect of PRL on LH pulsatility in female rats. Our findings characterize the role of E2 in the PRL modulation of hypothalamic components of the gonadal axis and LH release, demonstrating that E2 potentiates but is not essential for the suppression of pulsatile LH secretion caused by hyperprolactinemia.
高泌乳素血症通过抑制促性腺激素释放激素 (GnRH) 和黄体生成素 (LH) 的分泌导致不孕。由于催乳素 (PRL) 对下丘脑的作用通常需要雌二醇 (E2)，我们研究了 E2 在 PRL 诱导的 LH 脉冲抑制中的作用。接受油或 E2 治疗的去卵巢 (OVX) 大鼠 (OVX+E2) 在通过酶联免疫吸附试验连续测量尾血中的 LH 之前 30 分钟接受绵羊 PRL (oPRL) 皮下注射。E2 减少了 LH 脉冲分泌。1.5mg/kg 的 oPRL 进一步降低了 OVX+E2 中的 LH 脉冲频率，但对 OVX 大鼠没有影响。更高剂量的 6mg/kg oPRL 降低了 OVX 和 OVX+E2 大鼠的 LH 脉冲频率，而脉冲幅度和平均 LH 水平仅在 OVX+E2 大鼠中降低。OVX+E2 大鼠弓状核 (ARC) 的 kisspeptin 免疫反应性和 Kiss1 信使 RNA (mRNA) 水平降低。oPRL 降低了 OVX 大鼠 ARC 中的 kisspeptin 肽和基因表达，但没有改变 OVX+E2 大鼠中已经较低的水平。在腹前脑室核，oPRL 没有改变 kisspeptin 免疫反应性，并且矛盾的是，仅在 OVX+E2 大鼠中增加了 Kiss1 mRNA。此外，oPRL 有效降低了 Gnrh 表达，无论 E2 治疗如何。在这项研究中，我们使用尾尖采血来确定 PRL 对雌性大鼠 LH 脉冲性的急性影响。我们的发现描述了 E2 在 PRL 调节性腺轴和 LH 释放的下丘脑成分中的作用，表明 E2 增强但不是必需的，以抑制由高泌乳素血症引起的脉冲性 LH 分泌。
