Moore Joseph P, Wilson Lisa, Dalkin Alan C, Winters Stephen J
Division of Endocrinology & Metabolism, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
Biol Reprod. 2003 Jul;69(1):234-41. doi: 10.1095/biolreprod.102.012757. Epub 2003 Mar 19.
The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to differentially regulate the expression of the gonadotropin subunit genes in cultures of rat pituitary cells. PACAP is expressed within the hypothalamus, and concentrations of PACAP are 2- to 4-fold higher in the portal circulation than in the general circulation. Therefore, PACAP is a candidate regulator of pituitary function. In the present study, we examined the expression of PACAP mRNA within the paraventricular nucleus (PVN) during maturation (Days 20-60) in the male rat and compared this expression to the levels of the gonadotropin subunits, follistatin, and GnRH-receptor mRNAs within the anterior pituitary. Serum concentrations of FSH and LH confirm the established maturational pattern of divergent secretion of LH and FSH. Northern analysis of the gonadotropin subunit mRNAs revealed that FSHbeta expression parallels FSH secretion whereas LHbeta mRNA concentrations do not change during development. Expression of the GnRH receptor in the pituitary parallels that of FSHbeta. In situ hybridization revealed a developmental pattern of PACAP mRNA within the PVN that is reciprocal to that of FSHbeta. Competitive reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of total pituitary follistatin mRNA revealed no significant changes; however, semiquantitative RT-PCR analyses revealed the presence of two follistatin mRNA species, one of which, corresponding to follistatin-288, was developmentally regulated. These studies identified a reciprocal relationship between PVN PACAP and FSHbeta gene expression in maturing rats. We propose that PACAP contributes to the selective regulation of FSHbeta expression during maturation in the male rat, perhaps via regulation of follistatin.
神经肽垂体腺苷酸环化酶激活多肽(PACAP)已被证明在大鼠垂体细胞培养物中对促性腺激素亚基基因的表达具有不同的调节作用。PACAP在下丘脑中表达,其在门脉循环中的浓度比体循环中高2至4倍。因此,PACAP是垂体功能的候选调节因子。在本研究中,我们检测了雄性大鼠成熟过程中(第20至60天)室旁核(PVN)内PACAP mRNA的表达,并将其与垂体前叶中促性腺激素亚基、卵泡抑素和GnRH受体mRNA的水平进行比较。血清FSH和LH浓度证实了LH和FSH分泌差异的既定成熟模式。对促性腺激素亚基mRNA的Northern分析显示,FSHβ的表达与FSH分泌平行,而LHβ mRNA浓度在发育过程中没有变化。垂体中GnRH受体的表达与FSHβ的表达平行。原位杂交显示PVN内PACAP mRNA的发育模式与FSHβ的相反。对垂体总卵泡抑素mRNA的竞争性逆转录聚合酶链反应(RT-PCR)分析显示没有显著变化;然而,半定量RT-PCR分析显示存在两种卵泡抑素mRNA,其中一种对应于卵泡抑素-288,受发育调节。这些研究确定了成熟大鼠PVN中PACAP与FSHβ基因表达之间的反向关系。我们提出,PACAP可能通过调节卵泡抑素,在雄性大鼠成熟过程中对FSHβ表达的选择性调节起作用。