Linked Life Data

6406206

Source:http://linkedlifedata.com/resource/pubmed/id/6406206

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1983-7-8
pubmed:abstractText
The reduction of plasma testosterone (T) in male rats treated with 4-aminopyrazolo(3,4-d)pyrimidine (4-APP) has been recently shown to be associated with a fall in plasma LH, and appears to be secondary to this impairment of gonadotropin secretion rather than to the decrease in lipoprotein cholesterol caused by the adenine analog. The effects of 4-APP on pituitary function and the mechanism of the fall in gonadotropin secretion were analyzed in adult male rats treated ip with 5, 10, 25, and 50 mg 4-APP/kg BW for 3 days. Twenty four hours later, serum cholesterol levels were reduced by 68 +/- 5% (mean +/- SE) in animals treated with 5 mg 4-APP/kg BW and by up to 84 +/- 1% after higher doses. Basal levels of serum T were not affected by 5 mg/kg APP but were significantly reduced by higher doses (P less than 0.05). Serum T responses to human CG (100 IU) stimulation in APP-treated rats were reduced in absolute magnitude, but were enhanced in terms of percentage increase above baseline. The three highest doses of 4-APP reduced serum levels of LH (51-79%) and FSH (21-39%). However, serum gonadotropin responses to GnRH stimulation were augmented by 32 +/- 9% for LH and 27 +/- 12% for FSH after 4-APP treatment. Serum levels of TSH were significantly (P less than 0.05) reduced by 25 and 50 mg/kg 4-APP and serum PRL was lowered by only the higher dose. Serum GH was lowered and ACTH increased by 5 mg/kg 4-APP. The pituitary contents of LH, FSH, and TSH were unchanged after 4-APP treatment, but PRL and GH contents were slightly but significantly increased (P less than 0.05). Pituitary receptors for GnRH (88 +/- 14 fmol/mg protein) were reduced by in vivo treatment with 25 and 50 mg/kg 4-APP to 52 +/- 5 and 57 +/- 7 fmol/mg, but not by 10 mg/kg 4-APP. No change in pituitary GnRH receptor content was observed after 48-h exposure to 10(-7) or to 10(-5) M 4-APP in vitro. The medial hypothalamic GnRH content was unchanged by 4-APP treatment. The dissociated effects of 4-APP on serum cholesterol and T levels, and the maintenance of T responses to human CG, provide further evidence that testicular androgen biosynthesis is not solely dependent on circulating cholesterol. The greater sensitivity of pituitary gonadotropins to 4-APP inhibition is evidence for a selective action of this drug on pituitary hormone release in vivo. Although the hypothalamic content of GnRH was unaltered by 4-APP treatment, the decrease in pituitary GnRH receptors observed in vivo, together with the fall in circulating LH and FSH and retention of gonadotropin responses to GnRH stimulation, suggest that the primary effect of 4-APP is to inhibit GnRH synthesis and/or release from the hypothalamus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1973-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
Inhibition of pituitary gonadotropin secretion by 4-aminopyrazolo(3,4-d) pyrimidine.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.