• Mahesh, Virendra (PI)
  • Brann, Darrell W (PI)
  • Mahesh, Virendra (PI)
  • Mahesh, Virendra (PI)

Project: Research project

Project Details


The steroidal modulation of FSH and LH secretion is an important area of
study for a full understanding of the control of ovulation. The immature
female rat castrated on Day 26 of age and primed with 0.1 Mug/kg BW of
estradiol will be used to study the effects of 20 Alpha; 5 Alpha; 20 Alpha;
3 Alpha; 5 Alpha; 20 Alpha; and 3 Beta, 5 Alpha-reduced metabolites of
progesterone on FSH and LH secretion. The selective release of FSH by 5
Alpha-dihydroprogesterone and selective release of LH by 3 Alpha-hydroxy-5
Alpha-pregnant-20-one will be confirmed in the 21-day-old rat injected with
pregnant mare's serum gonadotropin. The requirement for 5 Alpha-reduction
of progesterone for FSH release will be tested by using a 5 Alpha-reductase
inhibitor. The effect of progesterone metabolites on hypothalamic LHRH
secretion will be evaluated by measuring medial basal hypothalamic,
preoptic area, and plasma LHRH levels along with serum LH and FSH levels at
15 min intervals after injecting the progestin in estrogen-primed castrated
rats. The direct effect of progesterone and its metabolites on the
pituitary will be determined by studying the effect of the steroids on
cellular content and basal and LHRH stimulated release of LH and FSH in
dispersed pituitary monolayer cell cultures. The separation of various
gonadotroph populations will be attempted by using unit gravity and Percoll
gradient techniques. The time course of progesterone effects on anterior
pituitary nuclear estrogen receptors will be studied at 1, 2, 3, 4, 8 and
12 hrs after the progesterone injection in vivo and the effects of
progesterone metabolites on estrogen receptor dynamics will be evaluated.
The specificity of the effect of progesterone treatment of the nuclei or
cytosol in depleting nuclear estradiol receptors in vitro will be studied
by examining the effects of cholesterol, corticosterone and 5
Alpha-dihydrotestosterone. Whether transcription and/or protein synthesis
is involved in the action of progesterone in the reduction of occupied
nuclear estrogen receptors will be determined by using actinomycin-D and
cycloheximide. Experiments will be done to determine the interactive
effects of progesterone on estrogen receptors and estrogens on progesterone
receptors and to determine if progesterone modulates its own receptors. In
these studies, cytoplasmic and nuclear estradiol and progesterone receptors
will be measured after treatment of castrated rats with various estrogen
and progesterone regimens.
Effective start/end date12/1/8111/30/99


  • Eunice Kennedy Shriver National Institute of Child Health and Human Development


  • Medicine(all)


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