MATURATION OF HYPOTHALAMIC-PITUITARY-GONADAL FUNCTION IN NORMAL HUMAN FETUSES - CIRCULATING LEVELS OF GONADOTROPINS, THEIR COMMON ALPHA-SUBUNIT AND FREE TESTOSTERONE, AND DISCREPANCY BETWEEN IMMUNOLOGICAL AND BIOLOGICAL-ACTIVITIES OF CIRCULATING FOLLICLE-STIMULATING-HORMONE
MATURATION OF HYPOTHALAMIC-PITUITARY-GONADAL FUNCTION IN NORMAL HUMAN FETUSES - CIRCULATING LEVELS OF GONADOTROPINS, THEIR COMMON ALPHA-SUBUNIT AND FREE TESTOSTERONE, AND DISCREPANCY BETWEEN IMMUNOLOGICAL AND BIOLOGICAL-ACTIVITIES OF CIRCULATING FOLLICLE-STIMULATING-HORMONE
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DOI：
10.1210/jcem-73-3-525
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发表时间：
1991-09-01
影响因子：
5.8
通讯作者：
BEITINS, IZ
中科院分区：
文献类型：
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作者：
BECKPECCOZ, P;PADMANABHAN, V;BEITINS, IZ
最近可用的脐带穿刺（一种低风险和有效的胎儿血液取样技术）和超灵敏/高特异性的双位点免疫荧光测定法（IFMA）用于垂体和绒毛膜糖蛋白激素（I-LH， I-FSH和I-CG）的测量，促使我们研究了114例妊娠17-40周的正常人类胎儿（49例女性和65例男性）的下丘脑-垂体-性腺功能成熟。从216例连续的cordocentes中选择受试者进行快速核型和胎儿感染或血液系统疾病的诊断。此外，采用大鼠支持细胞芳香酶诱导法测定FSH生物活性（B-FSH）， RIA法测定糖蛋白激素α -亚基（α -su），直接模拟法测定循环游离睾酮（fT）。不同测量方法均未发现明显的交叉反应。特别是，α - su不干扰任何IFMA， CG在LH IFMA中的交叉反应性为0.5%。妊娠17-24周时，女性胎儿的循环I-LH、I-FSH和B-FSH水平明显高于男性胎儿（I-LH， 48 +/- 4比6.3 +/- 0.7 U/L; I-FSH， 35 +/- 2比0.7 +/- 0.1 U/L; B-FSH， 131 +/- 17比43.4 +/- 5.4 U/L）。在妊娠最后几周，女性和男性胎儿的I-LH和I-FSH水平均显著下降（I-LH为0.24 +/- 0.05和1.0 +/- 0.3 U/L； I-FSH为0.45 +/- 0.1和0.5 +/- 0.1 U/L），而血清B-FSH仍然升高，但先前记录的性别差异消失（54.3 +/- 7.2和58.7 +/- 7.3 U/L）。妊娠中期女性和男性胎儿的循环I-CG和α - su水平均升高（I-CG分别为117 +/- 29和191 +/- 44 U/L； α - su分别为143 +/- 16和105 +/- 9 μ g/L），此后下降（I-CG为42 +/- 9和26 +/- 6 U/L； α - su为60 +/- 15和37 +/- 6 μ g/L）。妊娠中期女性血清f - T水平显著低于男性（4.3 +/- 0.9 vs. 10.0 +/- 0.8 pmol/L），直至足月，性别差异消失（16.2 +/- 1.8 vs. 17.6 +/- 1.6 pmol/L）。目前的数据显示：1)妊娠中期胎儿下丘脑-垂体-性腺成熟的特征是I-LH、I-FSH和f - T分泌有明显的性别差异，f - T的增加导致妊娠晚期促性腺激素分泌阻滞；2)证实妊娠中期胎儿循环I-CG水平明显升高，随后下降；3)两性胎儿循环α - su大量过剩。它们的水平比预期的与完全糖蛋白激素一起分泌的水平高10- 15倍。4)首次证明男性和女性的B-FSH水平都高于I-FSH水平。虽然这种FSH样物质的来源和生物化学仍有待阐明，但具有更高生物活性的FSH分子的分泌可能确保胎儿期性腺的维持和生长。
The recent availability of both cordocentesis, a low risk and effective technique for fetal blood sampling, and ultrasensitive/highly specific two-site immunofluorometric assays (IFMA) for pituitary and chorionic glycoprotein hormone (I-LH, I-FSH, and I-CG) measurement prompted us to study the maturation of hypothalamic-pituitary-gonadal function in 114 normal human fetuses (49 females and 65 males) from 17-40 weeks gestation. The subjects were selected from 216 consecutive cordocenteses carried out for rapid karyotyping and diagnosis of fetal infection or hematological disorders. In addition, FSH bioactivity (B-FSH) was measured by rat Sertoli cell aromatase induction assay, glycoprotein hormone alpha-subunit (alpha-SU) by RIA, and circulating free testosterone (fT) by direct analog technique. No significant cross-reactions were recorded in the different measurement methods. In particular, alpha-SU did not interfere in any IFMA, and CG cross-reactivity in LH IFMA was 0.5%. Circulating I-LH, I-FSH, and B-FSH levels at 17-24 weeks gestation were significantly higher in female than in male fetuses (I-LH, 48 +/- 4 vs. 6.3 +/- 0.7 U/L; I-FSH, 35 +/- 2 vs. 0.7 +/- 0.1 U/L; B-FSH, 131 +/- 17 vs. 43.4 +/- 5.4 U/L). During the last weeks of gestation, a significant decrease in I-LH and I-FSH levels was seen in both female and male fetuses (I-LH, 0.24 +/- 0.05 and 1.0 +/- 0.3 U/L; I-FSH, 0.45 +/- 0.1 and 0.5 +/- 0.1 U/L), while serum B-FSH remained elevated, but the previously recorded difference between sexes disappeared (54.3 +/- 7.2 and 58.7 +/- 7.3 U/L). Circulating I-CG and alpha-SU levels at midgestation were elevated in both female and male fetuses (I-CG, 117 +/- 29 and 191 +/- 44 U/L; alpha-SU, 143 +/- 16 and 105 +/- 9-mu-g/L, respectively) and decreased thereafter (I-CG, 42 +/- 9 and 26 +/- 6 U/L; alpha-SU, 60 +/- 15 and 37 +/- 6-mu-g/L). Serum f T levels at midgestation were significantly lower in females than in males (4.3 +/- 0.9 vs. 10.0 +/- 0.8 pmol/L) and increased until term, when the difference between sexes disappeared (16.2 +/- 1.8 vs. 17.6 +/- 1.6 pmol/L).The present data 1) show that a clear sex difference in I-LH, I-FSH, and f T secretion characterizes fetal hypothalamic-pituitary-gonadal maturation at midgestation and that the increase in f T contributes to gonadotropin secretion blockade during the third trimester of pregnancy, 2) confirm that circulating I-CG levels are clearly elevated at midgestation and decrease thereafter, 3) show that in fetuses of both sexes, there is an enormous excess of circulating alpha-SU, the levels of which are 10- to 15-fold higher than those expected to be secreted along with complete glycoprotein hormones, and 4) demonstrate for the first time that B-FSH levels in both males and females are higher than those of I-FSH. Although the source and biochemistry of this FSH-like material remain to be elucidated, the secretion of FSH molecules with increased bioactivity may assure gonadal maintenance and growth during fetal life.