Effects of ovarian steroids upon responses mediated by adrenoceptors in separated layers of the myometrium and in the costo‐uterine muscle of the guinea‐pig

Abstract

1This study describes the effects of ovarian steroid hormones upon the responses to adrenoceptor agonists of isolated myometrium, separated into its longitudinal and circular layers, and of costo-uterine muscle from guinea-pigs. The preparations were field-stimulated at 100s intervals, and the adrenoceptor agonists phenylephrine and isoprenaline produced enhancement or inhibition of the evoked contractions. 2 Isoprenaline produced propranolol-sensitive inhibitory effects in longitudinal and circular myometrium and costo-uterine muscle preparations from animals from all experimental groups: i.e. from nonsteroid-treated animals (ovariectomized and intact); intact animals treated with either oestrogen or progesterone alone; ovariectomized animals treated with oestrogen; ovariectomized and intact animals treated with progesterone following oestrogen priming; and from animals 1-4 days post-partum. Longitudinal myometrial preparations from progesterone-treated oestrogenprimed and from post-partum animals were most sensitive to this agonist. 3 Phenylephrine produced phentolamine-sensitive excitatory effects in circular myometrial and costo-uterine muscle preparations from animals from all the experimental groups. In contrast, propranolol-sensitive inhibitory responses to phenylephrine occurred in longitudinal myometrial preparations taken from animals treated with progesterone following oestrogen priming, and from post-partum animals. Longitudinal myometrium from animals from the remaining experimental groups exhibited phentolamine-sensitive excitatory responses to phenylephrine. 4 The basis for the selective effect upon the longitudinal myometrium of exposure to progesterone following a period of oestrogen priming, is discussed. The results described are consistent with the possibility that in the longitudinal layer of guinea-pig uterus exposed to progesterone following oestrogen priming there is an increase in the proportion of P-adrenoceptors in this layer. This increase may reduce the likelihood of contractions arising via direct stimulation of oa-adrenoceptors in this layer in response to sympathetic activation during pregnancy.

The actions of histamine on the separated layers of the guinea-pig uterus: the influence of ovarian steroids

“…After one complete oestrous cycle had been monitored, as described by Farrar et al [10], guinea-pigs were used on day 6-10 (dioestrus) of the oestrous cycle (group 1) or treated with steroids as described previously [4]. Thus one group (group 2) received thrice weekly injections of oestradiol cypionate (20 ~tg/kg s.c. in 0.05-0.1 ml peanut oil) for 14 days before use and another group (group 3) received identical treatment with oestradiol cypionate, and in addition were given progesterone (3 mg/animal s.c. in 0.1 ml peanut oil) daily for 4-5 days before use.…”

“…Each horn was split open at the antimesometrial border and the endometrium gently scraped away with a scalpel blade. The two layers were separated and set up as described in [4] under 1.0 g tension in 30 ml organ baths containing the bathing medium described above, maintained at 37~ and bubbled with 57o COs in 02. Contractions were recorded isometrically using Grass FT03 transducers and recorded on Grass 7B polygraphs.…”

“…sensitive excitatory responses in both myometrial layers from virgin dioestrous and ovariectomised animals, but produces propranolol-sensitive inhibition of contractility of longitudinal but not circular myometrium from oestrogen-primed guinea-pigs treated with oestrogen and progesterone [4]. Our aim in this study was to determine whether the effects of histamine might also differ in the two myometrial layers, and/or might be selectively modulated by ovarian steroids.…”

“…However, there have been no reports of the effects of histamine upon the separated circular and longitudinal layers of the guinea-pig. In a series of experiments from this laboratory [4][5][6][7] we found that pregnancy and ovarian steroids have a marked effect to modulate the effects of sympathomimetic amines upon the longitudinal myometrium of this species. For example, phenylephrine causes phentolaminei To whom reprint requests should be addressed.…”

“…There is some evidence for a steroid-induced effect on the potency of histamine upon the longitudinal layer: Ponce-Monter et al [3] found that uterine horns from pregnant guinea-pigs are less sensitive to histamine than are those from dioestr6us guineapigs. We have examined the responses to histamine on the two my0metrial layers by constructing concentration-response curves upon field-stimulated preparations ofmyometrium from guinea-pigs receiving steroid treatments identical with those which modulate responsiveness to sympathomitactic amines [4][5][6][7], In addition, we have examined the effects of the histamine Hi-receptor antagonist, mepyramine and of the histamine H2-receptor antagonist, metiamide, using the pA2 method described by Arunlakshana & Schild [8], to determine whether the Hi-histamine receptor subtype mediating contraction in the tissue [9] is influenced by steroid treatment. This seemed possible since Goyal & Verma [2] have described experiments with Ha-and H2-histamine-receptor selective agonists and antagonists which indicate that H2-as well as Hi-histamine receptors mediate contractions of uterine horns from stilboestrol-treated guinea-pigs.…”