During the first pregnancy, guinea pig myometria show a loss of pre-junctional/post-ganglionic sympathetic nerve terminals. This is accompanied by post-junctional up-regulation of beta-adrenoreceptor (beta-AR) and adenylate cyclase (AC) function. These changes are only partially reversed in the postpartum period. Although progesterone (P) alone has been indirectly implicated in causing pre-junctional sympathectomy in nonpregnant guinea pigs, it is not known whether P or estradiol (E2) may directly influence myometrial beta-AR function in addition to or instead of pre-junctional sympathectomy. To answer this question, animals will be divided into two groups, (1) those which will receive exogenous P/E2 and (2) those in which P/E2 withdrawal will be effected. Uteri will be obtained from (a) normally cycling and oophorectomized, virgin, nonpregnant guinea pigs with or without P/E2 supplementation and (b) pregnant guinea pigs at 0.31, 0.67, and 1.00 of gestation (term 65-67 days) and in the postpartum period (term labor). Premature labor will be induced by oophorectomy at 0.31 gestation. Beta-AR properties in myometrial plasma membranes will be studied by (1) in vitro radioligand binding experiments using a specific beta-AR antagonist, 125I-HYP, as the probe; (2) measurement of AC activity. The pre-junctional properties will be examined by measuring in vitro catecholamine synthesis and content in tissue slices incubated in media containing 3H-tyrosine, or 3H-DOPA as precursors. Newly synthesized 3H-norepinephrine and dopamine will be monitored employing HPLC-EC. This project will significantly improve our understanding on the direct or indirect hormonal control of myometrial beta-AR function. In addition, since beta-AR regulate myometrial contractility, their up-regulation, is important for uterine quiescence and pregnancy maintenance while their down-regulation may allow for the occurrence of term and pre-term labor. Finally, the pregnant (and nonpregnant) guinea pig appear to be very similar, in terms of myometrial sympathetic nervous system function, to the human. Thus, observations obtained in this species can be logically extended to human pregnancies. This would be a significant contribution to our understanding of mechanisms controlling preterm (and term) labor.
| Hatjis, C G; Grogan, D M; Koritnik, D R (1989) Treatment of oophorectomized guinea pigs with intrauterine 17 beta-estradiol pellets may modulate myometrial beta-adrenergic receptor binding properties. Am J Obstet Gynecol 161:1628-32 |
| Hatjis, C G; Grogan, D M (1989) Pregnancy-induced changes in the interaction of guinea pig myometrial beta-adrenergic receptors with l-isoproterenol. Am J Obstet Gynecol 161:1633-6 |
| Hatjis, C G; Crews, A (1988) Regulation of guinea pig myometrial beta-adrenoreceptors by guanosine triphosphate and magnesium ion. Biol Reprod 38:522-7 |
| Hatjis, C G; Koritnik, D R; Crews, A (1988) Up-regulation of guinea pig myometrial beta-adrenoreceptors by systemic estradiol and progesterone. Endocrinology 122:1455-9 |
| Hatjis, C G (1986) Forskolin: unique diterpene activator of adenylate cyclase in pregnant and nonpregnant guinea pig myometrial membranes. Am J Obstet Gynecol 155:1202-8 |
