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The hormone 1α,25(OH) 2 vitamin D 3 (1,25-D) produces biological responses via both genomic and rapid mechanisms. The genomic responses are linked to a nuclear receptor, while the rapid responses are believed to utilize other signal transduction pathways that are likely linked to a putative cell membrane receptor for 1,25-D. The natural seco-steroid, 1,25-D, is capable of facile rotation...
Aldosterone at normal physiological levels induces rapid increases in intracellular calcium and pH in human distal colon. The end target of these rapid signaling responses are basolateral K + channels. Using spectrofluorescence microscopy and Ussing chamber techniques, we have shown that aldosterone activates basolateral Na/H exchange via a protein kinase C and calcium-dependent signaling...
A comparison of the interaction of 3β, 5α-tetrahydrodeoxycorticosterone (TDOC) on voltage-gated Ca 2+ - and the γ-aminobutyric receptor (GABA A ) gated-Cl - -channels was examined in freshly dissociated guinea-pig (GP) and rat hippocampal CA1 neurons and rat hypothalamic ventromedial nucleus (VMN) neurons. The steady-state inhibition of the peak Ca 2+ channel...
The focus of our work on rapid actions of estrogens has been on the immuno-identification of a membrane version of the estrogen receptor-α (mERα) and the correlation of the presence of this receptor to the rapid secretion of prolactin in pituitary tumor cells. We demonstrated the mERα by both fluorescence and immuno-enzyme-cytochemistry and with both conventional and confocal microscopy in the cell...
The presence of the glucocorticoid (GC) receptor is required for GC-evoked apoptosis. However, the explicit mechanism of involvement of this receptor continues to be debated. Employing the murine (S-49) and human (CCRF-CEM) lymphoid cell lines, we demonstrated that this response requires a specialized form of the glucocorticoid receptor (GR) that resides in the plasma membrane (mGR). Our studies of...
Previous work from our laboratory demonstrated that 1,25(OH) 2 D 3 rapidly stimulated hydrolysis of membrane polyphosphoinositides (PI) in rat colonocytes and in Caco-2 cells, generating the second messengers DAG and IP 3 . [Ca 2+ ] i subsequently increased due to IP 3 -mediated release of intracellular Ca 2+ stores, and to Ca 2...
In addition to the well-known genomic effects of steroid molecules via intracellular steroid receptors, certain steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. Several of these steroids accumulate in the brain after local synthesis or after metabolism of adrenal steroids. The 3α-hydroxy ring A-reduced pregnane steroids allopregnanolone and...
1,25-(OH) 2 D 3 (1,25) exerts its effects on growth plate chondrocytes through classical vitamin D (VDR) receptor-dependent mechanisms, resulting in mineralization of the extracellular matrix. Recent studies have shown that membrane-mediated mechanisms are involved as well. 1,25 targets cells in the prehypertrophic and upper hypertrophic zones of the costochondral cartilage growth...
It is known that steroids can induce cell surface receptor aggregation followed by activation of receptor and nonreceptor tyrosine kinases. It has been shown recently that 17β-estradiol (E 2 ) can stimulate the Src/p21 ras /mitogen-activated protein kinase pathway in breast cancer cells, and this effect is supposed to mediate the E 2 -induced stimulation of breast...
17β-Estradiol (E 2 ) rapidly (<20 min) attenuates the ability of μ-opioids to hyperpolarize guinea pig hypothalamic neurons. We have used intracellular recordings from female guinea pig hypothalamic slices to characterize the receptor and intracellular pathway(s) mediating E 2 's rapid effects. E 2 acts stereospecifically with physiologically relevant concentration-dependence...
Stress-induced corticosterone (CORT) secretion that causes a rapid blockade of courtship clasping by male roughskin newts (Taricha granulosa) is mediated by a specific neuronal membrane receptor for CORT. Amplectic clasping, which can be triggered by pressure on the ventral body surface and cloaca, is controlled by the influence of medullary neurons on the spinal cord. Using clasping as a simple neurobehavioral...
Steroid hormones influence cell functions by binding to intracellular receptors and then acting within the nucleus. There is now evidence that steroids affect cell functions also via interaction with plasma membrane receptors in a number of different cell types. In this regard, progesterone appears to be one of the most active steroids. In this paper, we evaluate the effects of progesterone on rat...
Progesterone (P) is a physiological stimulus of human sperm functions. It is present in high levels at the site of fertilization (cumulus oophorus) and has been described to affect several sperm functions, including motility, capacitation, acrosome reaction, and the ability to bind and to respond to zona proteins. The effects of the steroid are mediated essentially by an increase of intracellular...
Estrogen is an important atheroprotective molecule that causes the rapid dilation of blood vessels by stimulating endothelial nitric oxide synthase (eNOS). There is also evidence that estrogen modulates airway epithelial NO production, thereby potentially affecting bronchial hyperresponsiveness. Studies in cultured endothelial and airway epithelial cells indicate that physiologic concentrations of...
Estrogen modulates a variety of functions, most of which can be explained by the classical genomic mechanism of action. However, a number of estrogen's actions appear to be incompatible with this mechanism and fall into the category of nongenomic. In the hippocampus, application of 17β-estradiol rapidly enhances the amplitude of kainate-induced currents of CA1 neurons. The potentiation resulted from...
Initiation of transcription is an early step in steroid hormone action. We investigated by means of atomic force microscopy (AFM) and fluorescence imaging the role of nuclear pore complexes (NPCs) in mediating signal transduction of the mineralocorticoid hormone aldosterone from the extracellular space into the cell nucleus. With AFM, we imaged single NPCs of isolated nuclear envelopes under native...
The genomic theory of steroid action has been the unquestioned dogma for the explanation of steroid effects over the past four decades. Despite early observations on rapid steroid effects being clearly incompatible with this theory, only recently has nongenomic steroid action been recognized more widely and led to a critical reappraisal of unsolved questions about this dogma. Evidence for nongenomic...
Progesterone rapidly increased intracellular free calcium ([Ca 2+ ] i ) in human sperm, removal of extracellular Ca 2+ prevented the increase in [Ca 2+ ] i . The Ca 2+ influx was not blocked by the T-type Ca 2+ channel blocker mibefradil. However T-type calcium channels do appear to be present in human sperm because the...
Meiosis in the amphibian oocyte is normally initiated by gonadotropins, which stimulate follicle cells to secret progesterone. The progesterone-induced G 2 /M transition in the amphibian oocyte was the first well-defined example of a steroid effect at the plasma membrane, since it could be shown that exogenous, but not injected, progesterone induced meiosis and that many of the progesterone-induced...
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