J Steroid Biochem Mol Biol. 1997 Apr;61(3-6):157-66.
Effect of estrogen deprivation on the reproductive physiology of male and female
primates.
Shetty G, Krishnamurthy H, Krishnamurthy HN, Bhatnagar S, Moudgal RN.
Center for Reproductive Biology and Molecular Endocrinology, Indian Institute of
Science, Bangalore.
The availability of CGS 16949A, CGS 20267 and CGP 47645, a series of aromatase
inhibitors (AIs) having high specific activity and specificity, made possible
this study wherein the need for estrogen (E) for regulating (a) follicular
maturation/ovulation, luteal function and pregnancy establishment, and (b)
testicular function of the bonnet monkey (Macaca radiata) has been examined.
Generally these compounds, used in the range of 500 microg to 2.5 mg/day did not
inhibit follicular maturation although they did reduce E levels. Although low
doses had no effect on ovulation it appears that relatively high doses of CGS
20267 and CGP 47645 could be inhibiting it. Three oral doses of letrozole (CGS
20267, each dose of 2 mg) during the follicular phase resulted in the formation
of multiple follicles in cycling females, and these could be ovulated by
exogenous hCG (1000 IU) treatment. Although administration of AI during the
early luteal phase had no effect on progesterone (P) production, it prevented
pregnancy establishment. Whereas AI administration in the female had no
significant effect on luteinizing hormone (LH) and follicle stimulating hormone
(FSH) levels (except at high drug dosages), it significantly increased serum
testosterone (T) levels in the male. Sustained high levels of T (30-50 ng/ml)
could be maintained for 100 days by administering 2.5 mg of CGP 47465 orally
once in 5 days. Blockade of E synthesis in the male led to the disruption of
testicular germ cell transformation, which in turn resulted in a significant
reduction in sperm production. These studies with aromatase inhibitors in the
monkey suggest that these compounds have a potential for use as fertility
regulating agents in both the male and female primate.
PMID: 9365186 [PubMed - indexed for MEDLINE]
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