Kerrigan J R, Martha P M, Krieg R J, Rogol A D, Evans W S
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908.
Endocrinology. 1989 Dec;125(6):3078-83. doi: 10.1210/endo-125-6-3078.
To investigate the role of somatostatin (SRIF) in regulating sexually dimorphic GH secretion, we used a reverse hemolytic plaque assay and acutely dispersed somatotropes from age-matched normal male, normal female, and androgen receptor-deficient, testicular feminized (Tfm) rats. Hemolytic plaques were developed after a 90-min incubation in the presence of GH antiserum, 10 nM GH-releasing hormone (GHRH), and the following concentrations of SRIF: 0, 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 nM. Additional studies were performed with 0 or 100 nM SRIF in the absence of GHRH. The absolute number of somatotropes (x10(6); mean +/- SEM) recovered from the pituitaries of Tfm rats (1.73 +/- 0.18) was significantly greater than that from the males (1.11 +/- 0.13; P = 0.01); the number from female rats (1.30 +/- 0.15) was not different from that of either male or Tfm animals. GHRH-stimulated GH secretion, as estimated by the mean GH plaque area (micron2 x 10(4); mean +/- SEM) in the absence of SRIF, was greater for somatotropes from male rats (3.36 +/- 0.41) than that for either Tfm (2.27 +/- 0.32; P = 0.02) or female (1.78 +/- 0.24; P = 0.001) rats; values for the latter two groups did not differ. However, mean GH plaque areas for each group during maximal SRIF inhibition in either the presence or absence of GHRH were indistinguishable from each other and from mean plaque areas obtained under basal conditions. As demonstrated by a lesser EC50 value (0.04 +/- 0.02 nM; mean +/- SEM), somatotropes from female rats were more sensitive to the inhibitory effect of SRIF than were those from either male (EC50 = 1.82 +/- 0.45; P = 0.0001) or Tfm (EC50 = 0.74 +/- 0.22, P = 0.0001) rats; values for the latter two groups were indistinguishable. These observed differences suggest that gender and/or the gonadal hormone environment may be important determinants of the inhibitory effects of SRIF on GH secretion by the somatotrope. While these gender-associated differences may represent effects of the gonadal hormones directly on the somatotrope, they could reflect modulation of the secretion of hypothalamic SRIF and/or GHRH by the prevailing gonadal hormone environment. Such gender-related differences may contribute to the overall sex-dependent patterns of GH secretion in the intact animal.
为研究生长抑素（SRIF）在调节生长激素（GH）分泌性别差异中的作用，我们采用反向溶血空斑试验，从年龄匹配的正常雄性、正常雌性以及雄激素受体缺陷的睾丸雌性化（Tfm）大鼠中急性分离出生长激素细胞。在存在GH抗血清、10 nM生长激素释放激素（GHRH）以及以下浓度的SRIF（0、0.001、0.003、0.01、0.03、0.1、0.3、1、3、10、30和100 nM）的情况下孵育90分钟后形成溶血空斑。在不存在GHRH的情况下，用0或100 nM SRIF进行了额外的研究。从Tfm大鼠垂体中回收的生长激素细胞的绝对数量（×10⁶；平均值±标准误）（1.73±0.18）显著高于雄性大鼠（1.11±0.13；P = 0.01）；雌性大鼠（1.30±0.15）的数量与雄性或Tfm动物的数量没有差异。在不存在SRIF的情况下，通过平均GH空斑面积（平方微米×10⁴；平均值±标准误）估计，GHRH刺激的GH分泌，雄性大鼠的生长激素细胞（面积为3.36±0.41）大于Tfm大鼠（2.27±0.32；P = 0.02）或雌性大鼠（1.78±0.24；P = 0.001）；后两组的值没有差异。然而，在存在或不存在GHRH的情况下，每组在最大SRIF抑制期间的平均GH空斑面积彼此之间以及与基础条件下获得的平均空斑面积没有区别。如通过较低的半数有效浓度（EC50）值（0.04±0.02 nM；平均值±标准误）所示，雌性大鼠的生长激素细胞对SRIF的抑制作用比雄性（EC50 = 1.82±0.45；P = 0.0001）或Tfm大鼠（EC50 = 0.74±0.22，P = 0.0001）更敏感；后两组的值没有区别。这些观察到的差异表明，性别和/或性腺激素环境可能是SRIF对生长激素细胞分泌GH抑制作用的重要决定因素。虽然这些与性别相关的差异可能代表性腺激素直接对生长激素细胞的作用，但它们可能反映了当前性腺激素环境对下丘脑SRIF和/或GHRH分泌的调节。这种与性别相关的差异可能有助于完整动物中GH分泌的整体性别依赖性模式。
