Inhibition of pituitary gonadotropin secretion by 4-aminopyrazolo(3,4-d) pyrimidine

Endocrinology
M S BlankM L Dufau

Abstract

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...Continue Reading

Citations

Jan 1, 1984·Journal of Steroid Biochemistry·M L DufauK J Catt
Jun 1, 1992·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·L K Malendowicz

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