Moore Joseph P, Winters Stephen J
Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
Biol Reprod. 2008 Apr;78(4):752-60. doi: 10.1095/biolreprod.107.065466. Epub 2007 Dec 26.
Pituitary Fshb concentrations increase markedly and selectively beginning on Postnatal Day 20 in the male rat. To evaluate the factors potentially responsible for this rise in FSH, we adjusted the time of weaning, which is generally also on Day 20. Male rat pups were provided nutrients by suckling only and were weaned to laboratory chow earlier (Day 17) or later (Day 23) than normally performed in animal facilities (Day 20). Between ages 17 and 29 days, significant increases were seen in serum LH (1.4-fold) and FSH (2.4-fold) levels; pituitary expression of Lhb (5.4-fold), Fshb (21.3-fold), and inhibin beta B (Inhbb, 2.26-fold) mRNAs; and testicular expression of Inhbb (10-fold) mRNA. Concurrently, significant decreases occurred in serum inhibin B levels (1.8-fold); pituitary adenylate cyclase-activating polypeptide (Adcyap1, 4.2-fold), total follistatin (Fst, 3.5-fold), and Fst isoform 288 (5.6-fold) mRNAs; and testicular expression of inhibin beta A (8.2-fold) mRNA. Early weaning significantly increased serum FSH but not LH and increased pituitary expression of Fshb and GnRH receptor (Gnrhr) mRNAs but not Lhb. Early weaning also significantly decreased serum inhibin B but increased testicular expression of the Inhbb subunit. Early weaning also caused pituitary expression of Fst and Adcyap1 to decline earlier than in the control group. Immediately after weaning, growth accelerated substantially, and the time of weaning produced significant and differential effects on circulating leptin levels that were not related to indices of FSH production. From these observations, we propose the novel hypothesis that the increase in growth rate subsequent to weaning signals circulating inhibin B levels to fall and pituitary Adcyap1 and consequently Fst expression to decrease, and that these events together facilitate the rise in Fshb and Gnrhr expression by increasing pituitary activin signaling.
雄性大鼠出生后第20天开始，垂体促卵泡激素β（Fshb）浓度显著且选择性地升高。为了评估可能导致FSH升高的因素，我们调整了断奶时间，断奶时间通常也在第20天。雄性幼鼠仅通过哺乳获取营养，并比动物设施中正常的断奶时间（第20天）更早（第17天）或更晚（第23天）断奶至实验室饲料。在17至29日龄之间，血清促黄体生成素（LH，1.4倍）和促卵泡激素（FSH，2.4倍）水平显著升高；垂体中促黄体生成素β（Lhb，5.4倍）、促卵泡激素β（Fshb，21.3倍）和抑制素βB（Inhbb，2.26倍）mRNA表达；以及睾丸中Inhbb（10倍）mRNA表达。同时，血清抑制素B水平显著降低（1.8倍）；垂体腺苷酸环化酶激活多肽（Adcyap1，4.2倍）、总卵泡抑素（Fst，3.5倍）和Fst同工型288（5.6倍）mRNA；以及睾丸中抑制素βA（8.2倍）mRNA表达。早期断奶显著增加血清FSH但不增加LH，并增加垂体中Fshb和促性腺激素释放激素受体（Gnrhr）mRNA表达但不增加Lhb。早期断奶还显著降低血清抑制素B，但增加睾丸中Inhbb亚基的表达。早期断奶还导致垂体中Fst和Adcyap1的表达比对照组更早下降。断奶后，生长立即大幅加速，断奶时间对循环瘦素水平产生显著且不同的影响，这与FSH产生指标无关。基于这些观察结果，我们提出了一个新的假设，即断奶后生长速率的增加信号使循环抑制素B水平下降，垂体Adcyap1以及随后Fst表达降低，并且这些事件共同通过增加垂体激活素信号传导促进Fshb和Gnrhr表达的升高。
