Molecular Mechanisms of Steroid Hormone Action in the Uterus

Jensen, Elwood V.

doi:10.1007/978-1-4613-0575-0_10

Cited by 4 publications

(2 citation statements)

References 343 publications

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“…Intracellular studies show th at oxytocin augm ents resting m em brane conductance (Suzuki & K uriyam a 1975) as well as profoundly altering the am plitude and frequency of m yom etrial contractions (K leinhaus & K ao 1969;Edw ards et al 1986). T he steroid horm ones, oestradiol and pro gesterone, can alter expression of proteins through their nuclear effects (Jensen 1990). Indeed, m R N A isolated from oestrogen-treated rat m yom etrium when expressed in Xenopus laevis oocytes gives rise to a voltage-dependent K + current thought to underlie the m arked hyperpolarization following oestrogen tre a t m ent (Boyle et al 1987).…”

Section: B)mentioning

confidence: 99%

Properties of large-conductance K ⁺ channels in human myometrium during pregnancy and labour

1993

Proc. R. Soc. Lond. B

102

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The conversion of the electrically silent pregnant uterus to highly excitable at term represents a dramatic physiological event which is poorly understood. Here we provide the first description, from single-channel recordings, of a large conductance (212 pS) calcium-activated potassium channel (BKCa) in human pregnant myometrium which, in labour tissue, is either absent or has been considerably altered in its physiological and pharmacological properties. In the latter, the K+ channels have an identical conductance (221 pS) and K+ selectivity to BKCa channels but exhibit no Ca2+ or voltage sensitivity. We have termed these BK channels. Furthermore, the activity of the BKCa channel from pregnant tissue is inhibited by internal application of Ba2+ but not tetraethylammonium (TEA), whereas the activity of the BK channel is sensitive to internal TEA but not Ba2+. The role of the BKCa channel may be to suppress myometrial activity during gestation whereas BK channel activity may be important in providing a Ca(2+)-independent K+ conductance which would allow cytoplasmic Ca2+ levels to rise without activating a counteracting Ca(2+)-dependent outward current, normally provided by the BKCa channels which, by its very nature, would tend to oppose depolarization. The findings suggest that K+ channels may have an important role in determining the functional activity of the myometrium.

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Section: B)mentioning

confidence: 99%

Properties of large-conductance K ⁺ channels in human myometrium during pregnancy and labour

1993

Proc. R. Soc. Lond. B

102

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“…However, the pendulum has shifted in favor of the belief-based on immunohistochemical techniques-that estrogen and progesterone receptors are strictly nuclear in localization, although a number of observations are more in tune with the classical two-step hypothesis (for references, see [38,39]). Whether the receptor in the soluble fraction (i.e., cytosolic fraction) is derived from the nucleus is still unsettled.…”

Section: Discussionmentioning

confidence: 95%

Comparison of Follicular Estrogen Receptors in Rat, Hamster, and Pig1

Kawashima

Greenwald

1993

Biology of Reproduction

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The hypophysectomized or intact hamster--unlike the rat--does not respond to estrogen by increasing the number of large antral follicles. In the pig, estrogen inhibits progesterone synthesis by granulosa cells from large follicles for 36 h before progesterone accumulation is enhanced. The objective of this study was to determine whether these divergent responses of the three species to estrogen are related to differences in follicular estrogen receptors. For the rat antral follicle, the equilibrium dissociation constants (Kds), expressed as nmol/L, were 0.55 +/- 0.07 in the cytosolic fraction and 0.46 +/- 0.11 in the nuclear fraction; for the hamster and pig follicles, the respective Kds were 1.08 +/- 0.04 and 0.94 +/- 0.11, and 1.16 +/- 0.23 and 1.09 +/- 0.17, respectively. The cytosolic and nuclear Kds for the rat follicle were statistically different from those of the other two species, but this is most likely not of biological consequence. Comparison of the maximal numbers of binding sites (NBSmax) in the cytosolic fractions of the antral follicles, expressed as fmol/mg protein, indicated a relationship of hamster > rat = pig; whereas in the nuclear fraction, with the NBSmax expressed as fmol/mg DNA, the relationship was hamster > pig > rat. The total number of estrogen receptors (sum of the NBSmax of cytosolic and nuclear fractions) was approximately tenfold higher in the hamster than in the rat. Thus, the failure of hamster large follicles to respond in vivo or in vitro to estrogen cannot be explained on the basis of lack of estrogen receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

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Response of primary rabbit kidney proximal tubule cells to estrogens

1999

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The effects of estrogens on the growth and function of primary rabbit kidney proximal tubule (RPT) cells have been examined in hormonally defined phenol red-free medium. 17beta-estradiol was observed to stimulate growth at dosages as low as 10(-10) M. The growth stimulatory effects of 17beta-estradiol were mitigated in the presence of hydrocortisone, suggesting that these two steroid hormones acted at least in part by common mechanisms. The effects of other steroids known to interact with the estrogen receptor were examined. Alpha estradiol was found to be growth stimulatory over a concentration range of 10(-9) to 10(-8) M, albeit to a lower extent than beta estradiol. In addition, the anti-estrogen tamoxifen was also growth stimulatory (unlike the case with the human mammary tumor cell line MCF-7). The effects of several metabolic precursors of 17beta-estradiol were examined, including testosterone, which was growth stimulatory, and progesterone, which was growth inhibitory. The growth stimulatory effects of 17beta-estradiol, alpha estradiol, and tamoxifen could possibly be explained by their interaction with an estrogen receptor. Indeed, metabolic labelling and immunoprecipitation studies indicated the presence of such an estrogen receptor in the primary cultures. The rate of biosynthesis of the estrogen receptor was found to be affected by the presence of exogenously added 17beta-estradiol. 17beta-estradiol was also observed to increase the activity of two brush border enzymes, alkaline phosphatase and gamma glutamyl transpeptidase, during the growth phase of the primary cultures.

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Molecular Mechanisms of Steroid Hormone Action in the Uterus

Cited by 4 publications

References 343 publications

Properties of large-conductance K ⁺ channels in human myometrium during pregnancy and labour

Properties of large-conductance K ⁺ channels in human myometrium during pregnancy and labour

Comparison of Follicular Estrogen Receptors in Rat, Hamster, and Pig1

Response of primary rabbit kidney proximal tubule cells to estrogens

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Molecular Mechanisms of Steroid Hormone Action in the Uterus

Cited by 4 publications

References 343 publications

Properties of large-conductance K + channels in human myometrium during pregnancy and labour

Properties of large-conductance K + channels in human myometrium during pregnancy and labour

Comparison of Follicular Estrogen Receptors in Rat, Hamster, and Pig1

Response of primary rabbit kidney proximal tubule cells to estrogens

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Product

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Properties of large-conductance K ⁺ channels in human myometrium during pregnancy and labour

Properties of large-conductance K ⁺ channels in human myometrium during pregnancy and labour