Linked Life Data

19293333

Source:http://linkedlifedata.com/resource/pubmed/id/19293333

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-4-23
pubmed:abstractText
We have characterized the in vivo actions of human wild-type FSH receptor (FSHR) overexpressed in Sertoli cells of transgenic (Tg) mice (TgFSHRwt) compared with transgenic overexpression of the human activated mutant FSHR*D567G (TgFSHR*D567G). Testicular TgFSHRwt expression significantly elevated specific FSH binding (>2-fold, P < 0.01) relative to nontransgenic testes, similar to increased FSH binding in TgFSHR*D567G testes. Isolated TgFSHRwt Sertoli cells exhibited higher FSH-stimulated cAMP levels compared with non-Tg or TgFSHR*D567G cells but did not display the elevated FSH-independent basal cAMP levels found in TgFSHR*D567G Sertoli cells. Furthermore, Sertoli cell overexpression of TgFSHR*D567G but not TgFSHRwt allowed promiscuous cAMP responses to human chorionic gonadotropin (300 IU/ml) and TSH (30 mIU/ml), demonstrating increased constitutive signaling and altered glycoprotein hormone specificity via the intracellular D567G substitution rather than FSHR overexpression. Despite elevating Sertoli cell FSH sensitivity, overexpression of TgFSHRwt had no detectable effect upon normal testis function and did not stimulate Sertoli and germ cell development in testes of gonadotropin-deficient hypogonadal (hpg) mice, in contrast to the increased meiotic and postmeiotic germ cell development in TgFSHR*D567G hpg testes. Increased steroidogenic potential of TgFSHR*D567G hpg testes was demonstrated by elevated Cyp11a1 and Star expression, which was not detected in TgFSHRwt hpg testes. Androgen-regulated and Sertoli cell-specific Rhox5 gene expression was increased in TgFSHR*D567G but not TgFSHRwt hpg testes, providing evidence of elevated LH-independent androgen activity due to mutant FSHR*D567G. Hence, transgenic FSHR overexpression in Sertoli cells revealed that the D567G mutation confers autonomous signaling and steroidogenic activity in vivo as well as promiscuous glycoprotein hormone receptor activation, independently of FSHR overexpression alone.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0193-1849
pubmed:author
pubmed:issnType
Print
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E1022-8
pubmed:meshHeading
pubmed-meshheading:19293333-Animals, pubmed-meshheading:19293333-Cholesterol Side-Chain Cleavage Enzyme, pubmed-meshheading:19293333-Cyclic AMP, pubmed-meshheading:19293333-Follicle Stimulating Hormone, pubmed-meshheading:19293333-Histocytochemistry, pubmed-meshheading:19293333-Humans, pubmed-meshheading:19293333-Male, pubmed-meshheading:19293333-Mice, pubmed-meshheading:19293333-Mice, Transgenic, pubmed-meshheading:19293333-Mutation, pubmed-meshheading:19293333-Organ Size, pubmed-meshheading:19293333-Phosphoproteins, pubmed-meshheading:19293333-RNA, Messenger, pubmed-meshheading:19293333-Receptors, FSH, pubmed-meshheading:19293333-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19293333-Sertoli Cells, pubmed-meshheading:19293333-Spermatogenesis, pubmed-meshheading:19293333-Testis
pubmed:year
2009
pubmed:articleTitle
Transgenic mutant D567G but not wild-type human FSH receptor overexpression provides FSH-independent and promiscuous glycoprotein hormone Sertoli cell signaling.
pubmed:affiliation
ANZAC Research Institute, Concord Hospital, Sydney NSW 2139, Australia. charles@anzac.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't