Alexander J M, Jameson J L, Bikkal H A, Schwall R H, Klibanski A
Neuroendocrine Unit, Massachusetts General Hospital, Boston 02114.
J Clin Endocrinol Metab. 1991 Jun;72(6):1261-7. doi: 10.1210/jcem-72-6-1261.
The effects of activin on pituitary FSH biosynthesis have been previously characterized using primary rat pituitary cultures; however, little is known of the effects of activin on FSH biosynthesis and secretion in human pituitary tissue. Production of intact glycoprotein hormones and free subunits is increasingly recognized in pituitary tumors; however, the regulation of gonadotropins in such tumors has not been addressed. We have investigated the effects of human recombinant activin on glycoprotein hormone biosynthesis and secretion in primary cultures of 12 human glycoprotein hormone-producing pituitary adenomas and compared this with the effects of activin in normal rat anterior pituitary cells. In 33% of the human pituitary tumors studied, significant (P less than 0.05) increases in FSH beta secretion occurred in response to incubation with 20 ng/mL activin for 24 h (19-287% stimulation), without changes in the production of intact FSH. A Northern analysis performed on cells derived from one tumor indicated that FSH beta mRNA levels increased 350% after activin treatments; however, FSH secretion did not parallel the mRNA changes. None of the human glycoprotein hormone-producing tumors significantly increased FSH secretion in response to activin. To validate the biological activity of recombinant human activin-A and to confirm time and dose conditions for the human tumor cultures, we also examined its ability to stimulate FSH production in rat pituitary cultures. Activin (20 ng/mL) added to the culture medium significantly increased FSH secretion and steady state levels of FSH beta mRNA after 24 h. These data indicate that some glycoprotein hormone-producing pituitary tumors treated with purified activin have discordant responses of intact gonadotropins and free subunit responses. In contrast to responses in normal rat gonadotrophs, FSH beta biosynthetic pathways may be uncoupled from intact FSH secretion in a subset of glycoprotein hormone-producing pituitary adenomas.
激活素对垂体促卵泡激素（FSH）生物合成的影响此前已通过原代大鼠垂体培养进行了表征；然而，关于激活素对人垂体组织中FSH生物合成和分泌的影响却知之甚少。垂体肿瘤中完整糖蛋白激素和游离亚基的产生越来越受到认可；然而，此类肿瘤中促性腺激素的调节尚未得到研究。我们研究了重组人激活素对12例产生人糖蛋白激素的垂体腺瘤原代培养物中糖蛋白激素生物合成和分泌的影响，并将其与激活素对正常大鼠垂体前叶细胞的影响进行了比较。在所研究的33%的人垂体肿瘤中，与20 ng/mL激活素孵育24小时后，FSHβ分泌显著增加（P<0.05）（刺激幅度为19 - 287%），而完整FSH的产生没有变化。对来自一个肿瘤的细胞进行的Northern分析表明，激活素处理后FSHβ mRNA水平增加了350%；然而，FSH分泌与mRNA变化并不平行。没有一例产生人糖蛋白激素的肿瘤对激活素产生显著的FSH分泌增加。为了验证重组人激活素 - A的生物活性并确定人肿瘤培养的时间和剂量条件，我们还检测了其刺激大鼠垂体培养物中FSH产生的能力。向培养基中添加激活素（20 ng/mL）24小时后，显著增加了FSH分泌和FSHβ mRNA的稳态水平。这些数据表明，一些用纯化激活素处理的产生糖蛋白激素的垂体肿瘤对完整促性腺激素和游离亚基的反应不一致。与正常大鼠促性腺细胞的反应不同，在一部分产生糖蛋白激素的垂体腺瘤中，FSHβ生物合成途径可能与完整FSH分泌解偶联。
