AMES DWARF MICE EXHIBIT SOMATOTROPE COMMITMENT BUT LACK GROWTH HORMONE-RELEASING FACTOR RESPONSE
AMES DWARF MICE EXHIBIT SOMATOTROPE COMMITMENT BUT LACK GROWTH HORMONE-RELEASING FACTOR RESPONSE
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DOI：
10.1210/en.136.3.1161
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发表时间：
1995-03-01
期刊：
影响因子：
4.8
通讯作者：
CAMPER, SA
中科院分区：
文献类型：
--
作者：
GAGE, PJ;LOSSIE, AC;CAMPER, SA
艾姆斯侏儒小鼠有一种隐性缺陷，导致受影响的小鼠（df/df）具有细胞极度减少的前垂体，通常缺乏促生长素、促乳素和促甲状腺素。我们报告检测罕见的GH（+）细胞灶的免疫细胞化学，这表明一些承诺的生长激素细胞的命运可以发生在DF/DF小鼠的垂体。GHRF在调节生长激素细胞增殖中的作用是有据可查的。已经表明，在转基因小鼠中表达人GHRF（hGHRF）导致与非转基因同窝出生小鼠相比增加的体细胞生长和生长激素细胞增生。为了评估个体发育过程中GHRF的过度表达是否可能引起df/df小鼠的生理反应，我们产生了表达hGhrf转基因的df/df小鼠。虽然转基因df杂合子的体细胞生长显着增加，非转基因同窝出生的，df/df小鼠难治性过量GHRF。没有GHRF受体（Grfr）转录检测DF/DF胎儿或成年小鼠原位杂交分析。相反，在df/ +小鼠中通过e16.5检测到Grfr表达。在df/df胎儿中缺乏Grfr表达可能是他们对GHRF缺乏反应的原因，并意味着elf基因产物在e16.5之前是必需的。
Ames dwarf mice have a recessive defect that results in affected mice (df/df) with extremely hypocellular anterior pituitaries that generally lack somatotropes, lactotropes,and thyrotropes. We report detection of rare foci of GH(+) cells by immunocytochemistry, suggesting that some commitment to a somatotrope cell fate can occur in the pituitaries of df/df mice. A role for GHRF in regulating somatotrope proliferation is well documented. It has been shown that expression of human GHRF (hGHRF) in transgenic mice resulted in increased somatic growth and somatotrope hyperplasia over nontransgenic littermates. To assess whether overexpression of GHRF during ontogeny might elicit a physiological response in df/df mice, we generated df/df mice expressing the hGhrf transgene. Although the somatic growth of transgenic df heterozygotes was dramatically increased over that of nontransgenic littermates, df/df mice were refractory to excess GHRF. No GHRF receptor (Grfr) transcripts were detectable in df/df fetuses or adult mice by in situ hybridization analysis. In contrast, Grfr expression is detected by e16.5 in df/ + mice. The lack of Grfr expression in df/df fetuses may account for their lack of response to GHRF and implies that the elf gene product is required before e16.5.