GROWTH HORMONE IN PITUITARY AND TESTICULAR FUNCTION

生长激素对垂体和睾丸功能的影响

• 批准号: 6084702
• 负责人: VARADARAJ CHANDRASHEKAR
• 金额: $ 10.58万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6084702
• 关键词: Leydig cells; androstenedione; dopamine agonists; estradiol; fertility; follicle stimulating hormone; genetically modified animals; growth hormone releasing hormone; hormone receptor; hormone regulation /control mechanism; inhibin; insulinlike growth factor; laboratory mouse; luteinizing hormone; male; northern blottings; pituitary gland; pituitary gonadal axis; progesterone; prolactin; radioimmunoassay; somatostatin; somatotropin; testis; testosterone

Re production is adversely affected in human acromegaly due to excess GH secretion. Also in men, congenital GH resistance is due to mutated GH receptors (Laron syndrome) is associated with delay in sexual maturation, suggesting a role of GH in reproduction. However, it is not know whether these changes are mediated via the pituitary gland. To address this issue, pituitary and testicular functions will be evaluated in GH receptor knockout (GHR-KO mice; a model for Laron syndrom) and transgenic mice expressing the human GHRH gene (GHRH mice; a model for acromegaly). In GHR-KO male mice, the LH response to GnRH treatment is testosterone concentrations are increased, whereas the LH response to GnRH treatment is decreased. The specific aims are to assess why the pituitary and testicular functions are altered in these two lines of mice. To evaluate whether the alterations in pituitary and testicular function are due to lack of IGF-I secretion, GHR-KO mice will be treated with IGF-I or to determine whether the effects are due to hyper prolactinemia, prolactin secretion will be suppressed by treatment with a dopamine agonist. To examine whether the increased circulating testosterone levels in GHRH mice is due to increased IGF-I secretion, these animals will be treated with somatostatin to suppress IGF-I secretion. In these experiments, the pituitary function will be evaluated by measuring the gonadotropin response to GnRH treatment and assess LHbeta and FSHbeta mRNA expressions in the pituitary gland. The testicular function will be determined by evaluating the testosterone and the testosterone precursor responses to LH treatment. The long-term goals are to examine the long-term effects of exogenous GH on reproduction in experimental animals. These studies may have some impact on the usage of GH in aging.

由于生长激素分泌过多，人类肢端肥大症的生殖受到不利影响。同样在男性中，先天性生长激素抵抗是由于生长激素受体突变（Laron综合征）与性成熟延迟有关，这表明生长激素在生殖中的作用。然而，尚不清楚这些变化是否通过脑垂体介导。为了解决这个问题，将在GH受体敲除（GHR-KO小鼠，Laron综合征模型）和表达人类GHRH基因的转基因小鼠（GHRH小鼠，肢端肥大症模型）中评估垂体和睾丸功能。在GHR-KO雄性小鼠中，LH对GnRH治疗的反应是睾酮浓度增加，而LH对GnRH治疗的反应降低。具体目的是评估为什么垂体和睾丸功能在这两种小鼠中被改变。为了评估垂体和睾丸功能的改变是否由于缺乏IGF-I分泌，GHR-KO小鼠将接受IGF-I治疗，或者为了确定这种影响是否由于高催乳素血症，催乳素分泌将被多巴胺激动剂治疗抑制。为了研究GHRH小鼠中循环睾酮水平的增加是否由于IGF-I分泌增加，这些动物将接受生长抑素治疗以抑制IGF-I分泌。在这些实验中，将通过测量促性腺激素对GnRH治疗的反应来评估垂体功能，并评估垂体中LHbeta和FSHbeta mRNA的表达。睾丸功能将通过评估睾酮和睾酮前体对LH治疗的反应来确定。长期目标是研究外源性生长激素对实验动物生殖的长期影响。这些研究可能对生长激素在衰老过程中的使用有一定的影响。

项目成果

The impact of altered insulin-like growth factor-I secretion on the neuroendocrine and testicular functions.

胰岛素样生长因子 I 分泌改变对神经内分泌和睾丸功能的影响。

• 发表时间: 2005
• 期刊: Minerva ginecologica.
• 作者: Chandrashekar,V;Bartke,A
• 通讯作者: Bartke,A

Puberty is delayed in male growth hormone receptor gene-disrupted mice.

• DOI: 10.1002/j.1939-4640.2002.tb02308.x
• 发表时间: 2002-09
• 期刊: Journal of andrology
• 作者: D. E. Keene;M. Suescun;Melissa G Bostwick;V. Chandrashekar;A. Bartke;J. Kopchick

Testicular endocrine function in GH receptor gene disrupted mice.

GH受体基因扰乱小鼠睾丸内分泌功能。

• DOI: 10.1210/endo.142.8.8298
• 发表时间: 2001
• 期刊: Endocrinology.
• 作者: Chandrashekar,V;Bartke,A;Awoniyi,CA;Tsai-Morris,CH;Dufau,ML;Russell,LD;Kopchick,JJ
• 通讯作者: Kopchick,JJ

The role of insulin-like growth factor-I in neuroendocrine function and the consequent effects on sexual maturation: inferences from animal models.

胰岛素样生长因子-I 在神经内分泌功能中的作用及其对性成熟的影响：来自动物模型的推论。

• 发表时间: 2003
• 期刊: Reproductive biology.
• 作者: Chandrashekar,Varadaraj;Bartke,Andrzej
• 通讯作者: Bartke,Andrzej