THE FREQUENCY OF GONADOTROPIN-RELEASING-HORMONE STIMULATION DIFFERENTIALLY REGULATES GONADOTROPIN SUBUNIT MESSENGER RIBONUCLEIC-ACID EXPRESSION
THE FREQUENCY OF GONADOTROPIN-RELEASING-HORMONE STIMULATION DIFFERENTIALLY REGULATES GONADOTROPIN SUBUNIT MESSENGER RIBONUCLEIC-ACID EXPRESSION
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DOI：
10.1210/endo-125-2-917
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发表时间：
1989-08-01
期刊：
影响因子：
4.8
通讯作者：
MARSHALL, JC
中科院分区：
文献类型：
--
作者：
DALKIN, AC;HAISENLEDER, DJ;MARSHALL, JC
已知下丘脑十肽GnRH调节垂体促性腺细胞合成和分泌LH和FSH。脉冲式GnRH分泌的频率变化，LH和FSH在不同的生理情况下有差异分泌。为了研究GnRH刺激频率改变在调节LH和FSH差异分泌中的潜在作用，我们检查了GnRH脉冲（25 ng/脉冲）以8-480 min的间隔给予去势睾酮替代大鼠的作用，以覆盖生理脉冲GnRH分泌的范围。快频率GnRH脉冲（8分钟脉冲间隔）增加α-亚单位mRNA浓度比盐水脉冲对照（对照，1.01 fmol cDNA结合/100 μ g垂体DNA）高3倍，LH βmRNA降低50%（对照，0.18 fmol cDNA结合），但FSH βmRNA无变化（对照，0.38 fmol cDNA结合）。每30分钟给予的GnRH脉冲增加了所有三种亚基mRNA（α，3倍，LH β，2倍; FSH β，2倍），急性LH释放和血清FSH浓度在此频率后达到最大值。较低频率的GnRH刺激（120至480分钟脉冲间隔）不改变α。和LH β。mRNA水平，但增加FSH β。mRNA 2- 2.5倍，FSH分泌得以维持。在24小时内以不同间隔给予GnRH的总剂量的均衡证实了亚基mRNA表达的频率依赖性。快频率GnRH刺激（8分钟）增加α。mRNA的1.5至2.5倍，而相同的总GnRH剂量是无效的，当在缓慢的频率（480分钟）。类似地，LH β. mRNA的增加，只有GnRH脉冲给予8分钟的时间间隔。相反，FSH β.每480分钟脉冲后mRNA增加2倍，8分钟脉冲间隔无效。数据表明，GnRH刺激的频率可以差异调节促性腺激素亚基mRNA的表达，并可能是一种机制，使一个单一的GnRH肽选择性地调节促性腺激素亚基基因的表达和激素分泌。
The hypothalamic decapeptide GnRH is known to regulate the synthesis and secretion of LH and FSH by pituitary gonadotrope cells. The frequency of pulsatile GnRH secretion changes and LH and FSH are differentially secreted in various physiological situations. To investigate the potential role of altered frequency of GnRH stimulation in regulating differential secretion of LH and FSH, we examined the effects of GnRH pulses (25 ng/pulse) were administered to castrate testosterone-replaced rats at intervals of 8-480 min to cover the range of physiological pulsatile GnRH secretion. Fast frequency GnRH pulses (8 min pulse intervals) increased .alpha.-subunit mRNA concentrations 3-fold above those in saline-pulsed controls (controls, 1.01 fmol cDNA bound/100 .mu.g pituitary DNA) and LH.beta. mRNA by 50% (controls, 0.18 fmol cDNA bound), but FSH.beta. mRNA was unchanged (controls, 0.38 fmol cDNA bound). GnRH pulses given every 30 min increased all three subunit mRNAs (.alpha., 3-fold, LH.beta., 2-fold; FSH.beta., 2-fold), and acute LH release and serum FSH concentrations were maximal after this frequency. Slower frequency GnRH stimuli (120- to 480-min pulse intervals) did not change .alpha. and LH.beta. mRNA levels, but increased FSH.beta. mRNA 2- to 2.5-fold, and FSH secretion was maintained. Equalization of the total dose of GnRH given at different intervals over 24 h confirmed the frequency dependence of subunit mRNA expression. Fast frequency GnRH stimuli (8 min) increased .alpha. mRNA 1.5 to 2.5-fold, while the same total GnRH doses were ineffective when given at slow frequency (480 min). Similarly, LH.beta. mRNA was only increased by GnRH pulses given at 8-min intervals. In contrast, FSH.beta. mRNA increased 2-fold after pulse given every 480 min, and the 8-min pulse interval was ineffective. The data show that the frequency of GnRH stimulation can differentially regulate gonadotropin subunit mRNA expression and may be a mechanism that enables a single GnRH peptide to selectively regulate gonadotropin subunit gene expression and hormone secretion.