Linked Life Data

7708066

Source:http://linkedlifedata.com/resource/pubmed/id/7708066

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1995-5-9
pubmed:abstractText
Transient transfection studies have proven useful in unraveling the molecular mechanisms underlying gonadotrope-specific expression and hormonal regulation of the gene encoding the alpha-subunit of the glycoprotein hormones. In contrast, similar studies performed with the LH beta gene have been less informative. When assayed by transient transfection into alpha T3-1 cells, activity of a 776-basepair bovine LH beta promoter-chloramphenicol acetyltransferase fusion gene (bLH beta CAT) was no greater than that of a promoterless control. To determine whether limited activity in vitro reflected the absence of critical regulatory elements, we examined activity of bovine LH beta fusion genes after stable integration in transgenic mice. In contrast to transient transfection studies, the LH beta promoter targeted high levels of CAT expression specifically to the pituitary. In addition, a bLH beta TK fusion gene was active only in gonadotropes. The bLH beta CAT transgene was also evaluated for responsiveness to gonadal steroids and GnRH. Testosterone and 17 beta-estradiol were capable of suppressing activity 70-80% in castrated males, despite the absence of high affinity binding sites for androgen or estrogen receptors. This suggests that feedback inhibition of LH beta CAT transgene expression by gonadal steroids may occur through an indirect mechanism, possibly at the level of the hypothalamus. To address whether the bLH beta CAT transgene could be regulated by GnRH, we treated ovariectomized females with antide, a GnRH antagonist. Antide suppressed transgene activity by 60%. Thus, the proximal promoter of the bovine LH beta subunit gene directs appropriate patterns of cell-specific expression and retains responsiveness to gonadal steroids and GnRH. In light of the robust activity of the LH beta promoter in transgenic mice, we suggest that this animal model can be exploited further to dissect the complex mechanisms that underlie gonadotrope-specific expression and hormonal regulation of the LH beta gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
1807-16
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7708066-Animals, pubmed-meshheading:7708066-Base Sequence, pubmed-meshheading:7708066-Cattle, pubmed-meshheading:7708066-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:7708066-Estradiol, pubmed-meshheading:7708066-Female, pubmed-meshheading:7708066-Gene Expression Regulation, pubmed-meshheading:7708066-Gonadotropin-Releasing Hormone, pubmed-meshheading:7708066-Luteinizing Hormone, pubmed-meshheading:7708066-Male, pubmed-meshheading:7708066-Mice, pubmed-meshheading:7708066-Mice, Transgenic, pubmed-meshheading:7708066-Molecular Sequence Data, pubmed-meshheading:7708066-Oligopeptides, pubmed-meshheading:7708066-Orchiectomy, pubmed-meshheading:7708066-Ovariectomy, pubmed-meshheading:7708066-Pituitary Gland, pubmed-meshheading:7708066-Promoter Regions, Genetic, pubmed-meshheading:7708066-Testosterone, pubmed-meshheading:7708066-Transfection
pubmed:year
1994
pubmed:articleTitle
The proximal promoter of the bovine luteinizing hormone beta-subunit gene confers gonadotrope-specific expression and regulation by gonadotropin-releasing hormone, testosterone, and 17 beta-estradiol in transgenic mice.
pubmed:affiliation
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't