Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1985-1-3
pubmed:abstractText
The sensitizing effect of oestrogens on GnRH-stimulated LH release was evaluated in pituitary cells from adult female rats, cultured for 2 days in the presence of 10(-13) to 10(-6) M concentrations of oestradiol and selected A- and D-ring modified oestrogens. With almost all steroids tested, bell-shaped dose-response curves with comparable LH-maxima but different ED max values were obtained for the LH response to a submaximal GnRH stimulus (5 X 10(-10) M). Maximal LH response to 5 X 10(-10) M GnRH were found at the following oestrogen concentrations: oestradiol and 4-hydroxyoestradiol = 10(-11) M; 2-methyloestradiol = 10(-9) M; 2-hydroxyoestradiol = 10(-8) M; with 4-methyloestradiol no significant maximum was observed. When cells were pretreated with 10(-13), 10(-11) and 10(-9) M oestradiol, or 4-hydroxyoestradiol, or 2-hydroxyoestradiol, and exposed to increasing concentrations of GnRH (10(-11) to 10(-7) M), an almost 10-fold decrease in the ED50 for GnRH was observed after pretreatment with 10(-11) M oestradiol and 4-hydroxyoestradiol. With 2-hydroxyoestradiol at this concentration, the sensitizing effect was much less pronounced. Increasing the steroid concentration to 10(-9) M slightly decreased the effect of oestradiol and 4-hydroxyoestradiol, whereas it increased the effect of 2-hydroxyoestradiol. Thus, at the target cell 4-hydroxyoestradiol has the same potency as oestradiol, while 2-hydroxyoestradiol is significantly less active. The sensitizing effect of oestradiol is only slightly decreased by the presence of a methyl group in position 2, but is markedly reduced by a methyl group in position 4. Our results also demonstrate the high sensitivity of the pituitary to oestrogen-induced enhancement of GnRH-stimulated gonadotrophin release, as well as the decrease of the positive effect at high oestrogen concentrations. The bell-shaped dose-response curves for oestrogen action should be taken into account when evaluating the effects of oestrogens and their derivatives upon gonadotrophin release from the pituitary gland.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0001-5598
pubmed:author
pubmed:issnType
Print
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
317-27
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Biphasic modulation of pituitary sensitivity to GnRH by oestrogens: the effects of A- and D-ring substitution on LH release in cultured pituitary cells.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't