Lee L R, Haisenleder D J, Marshall J C, Smith M S
Department of Physiology, University of Pittsburgh School of Medicine.
Endocrinology. 1989 Feb;124(2):776-82. doi: 10.1210/endo-124-2-776.
Pituitary GnRH receptor (GnRH-R) levels and LH secretion are suppressed in the lactating rat. To determine if LH synthesis is also inhibited, we have measured LH subunit mRNA levels in the pituitary of lactating rats. We have also examined the temporal relationship among restoration of GnRH-R, LH secretion, and LH synthesis after withdrawing the sensory stimulus of suckling. Pituitary alpha-subunit and LH beta mRNA levels were sharply reduced on day 10 of lactation in both intact and ovariectomized (OVX) animals compared with those in cycling diestrous rats or OVX controls. Removal of the suckling stimulus from OVX animals led to significant increases in alpha-subunit and LH beta mRNA levels by 24 h. Upon removal of the suckling stimulus from intact rats, alpha-subunit mRNA levels were restored by 48 h, but LH beta mRNA levels did not return to diestrous levels until 72 h. Pituitary GnRH-R levels were clearly up-regulated within 1 day after pup removal. Some LH pulses were observed by 48 h, but consistent plasma LH pulses were not detected until 72 h. When pulsatile GnRH was administered during the 24 h after pup removal from intact rats, the regimen of pulsatile GnRH was successful in inducing LH secretion; however, the restoration of pulsatile LH was not accompanied by increases in alpha-subunit and LH beta mRNA levels. The present studies provide further evidence to support the hypothesis that during lactation, the suppression of pituitary gonadotroph function is mainly due to the loss of hypothalamic GnRH secretion. Our data also show that 1) the restoration of GnRH-R alone is not sufficient to activate LH subunit mRNA and LH secretion; 2) the normal restoration of pulsatile LH secretion and increases in LH subunit mRNA are temporally correlated, as increases in LH secretion appear to precede increases in LH subunit mRNA; and 3) the restoration of pituitary LH subunit mRNA levels and pulsatile LH secretion took longer in the intact rat than in the OVX rat, suggesting that ovarian steroids may play a role in the inhibitory effect of lactation.
哺乳期大鼠的垂体促性腺激素释放激素受体（GnRH-R）水平和促黄体生成素（LH）分泌受到抑制。为了确定LH合成是否也受到抑制，我们测量了哺乳期大鼠垂体中LH亚基mRNA水平。我们还研究了停止哺乳的感觉刺激后，GnRH-R恢复、LH分泌和LH合成之间的时间关系。与处于动情间期的正常大鼠或卵巢切除（OVX）对照相比，完整和OVX动物在哺乳期第10天时垂体α亚基和LHβ mRNA水平均急剧降低。从OVX动物中去除哺乳刺激后，24小时内α亚基和LHβ mRNA水平显著升高。从完整大鼠中去除哺乳刺激后，48小时时α亚基mRNA水平恢复，但LHβ mRNA水平直到72小时才恢复到动情间期水平。去除幼崽后1天内垂体GnRH-R水平明显上调。48小时时观察到一些LH脉冲，但直到72小时才检测到持续的血浆LH脉冲。当从完整大鼠中去除幼崽后的24小时内给予脉冲式GnRH时，脉冲式GnRH方案成功诱导了LH分泌；然而，LH脉冲的恢复并未伴随着α亚基和LHβ mRNA水平的升高。本研究提供了进一步的证据支持以下假设：在哺乳期，垂体促性腺激素细胞功能的抑制主要是由于下丘脑GnRH分泌的丧失。我们的数据还表明：1）单独恢复GnRH-R不足以激活LH亚基mRNA和LH分泌；2）LH脉冲分泌的正常恢复和LH亚基mRNA的增加在时间上相关，因为LH分泌的增加似乎先于LH亚基mRNA的增加；3）完整大鼠垂体LH亚基mRNA水平和LH脉冲分泌的恢复比OVX大鼠所需时间更长，表明卵巢类固醇可能在哺乳期的抑制作用中发挥作用。
