Characterization and Hormonal Regulation of the Progesterone Receptor in the Endometrium and Myometrium of the Rabbit
Halstead, Julie A.
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Through much research it is now evident that steroid hormones interact with specific receptors in the cytoplasm of target tissues (Chan and 0'Malley, 1976). Furthermore, it has been shown that the steroid-receptor interaction is a prerequisite for the elicitation of a hormonal response. Progesterone, a female sex steroid hormone, has the primary function of preparing the uterus for blastocyst implantation and inhibiting uterine contractions in early pregnancy. The fact that progesterone plays such an indispensable role in early pregnancy implies that the elimination of the binding of progesterone with its cytoplasmic receptor might lead to a good method of fertility control. Current research is focusing on this area with attempts to discover an antiprogestin which has the capacity to bind to the specific progesterone receptors with high affinity, but which does not elicit the hormonal response characteristic of progesterone. Studies have been done with this end in mind using cytoplasmic progesterone receptors isolated from the entire uterus of various experimental animals. Uncertainty prevails however, as to whether the progesterone receptors are the same in the endometrial and myometrial tissues of the uterus. The importance of determining whether the progesterone receptors are similar in these two tissues lies in the fact that if the receptors are found to have different characteristics, one antiprogestin might not make an effective contraceptive agent, since in order to be totally effective this agent must suppress the progesterone response in both tissues of the uterus. The experiments which are dealt with in this paper were designed to discover if the specific cytoplasmic progesterone receptors in the endometrium and myometrium of the rabbit uterus are the same 1) in terms of their affinity for both natural and synthetic steroids, and 2) in terms of their hormonal regulation. An attempt was also made to determine what kind of steroid configuration contributes to an effective steroid-receptor interaction. The studies revealed that the progesterone receptors found in the endometrium and myometrium of rabbits are very similar in terms of their affinity for steroids. Furthermore, it was discovered that the steroid configuration which is best for binding has some sort of nonpolar carbon side group of limited size at C-17, no methyl group at C-10, and an A-ring with a ketone at C-3, a double bond at C-4, and no other additions. In terms of hormonal regulation the results showed that the progesterone receptors of the endometrium and myometrium are, in general, under the same dual hormonal regulation whereby estrogen causes an increase in receptor concentration and progesterone has the opposite effect. More specifically however, the progesterone receptors found in the endometrium appear to be regulated to a greater extent by estrogen and progesterone than the progesterone receptors in the myometrium.With honors.