ROLE OF HORMONE RECEPTORS

Lamb, T. D. and Pugh, Jr., E. N., G-protein cascades gains and kinetics, Trends Neurosci., 15, 291-299, 1992. Rodbell, M., The role of hormone receptors and GTP-regulatory proteins in membrane transduction, Nature, 284, 17-22, 1974. 

M. Rodbell, Role of Hormone Receptors and GTP-Regulatory Proteins in Membrane Transduction , Nature, 284, 17-22 (1980)... 

Tissue uptake of hormones the role of hormone receptors... 

Rodbell, M. (1980). The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature (London). 284, 17—22... 

The acute CNS effects of MDMA administration are mediated by the release of monoamine transmitters, with the subsequent activation of presynaptic and postsynaptic receptor sites.40 As specific examples in rats, MDMA suppresses 5-HT cell firing, evokes neuroendocrine secretion, and stimulates locomotor activity. MDMA-induced suppression of 5-HT cell firing in the dorsal and median raphe involves activation of presynaptic 5-HT1A autoreceptors by endogenous 5-HT.4142 Neuroendocrine effects of MDMA include secretion of prolactin from the anterior pituitary and corticosterone from the adrenal glands 43 Evidence supports the notion that these MDMA-induced hormonal effects are mediated via postsynaptic 5-HT2 receptors in the hypothalamus, which are activated by released 5-HT. MDMA elicits a unique profile of locomotor effects characterized by forward locomotion and elements of the 5-HT behavioral syndrome such as flattened body posture, Straub tail, and forepaw treading.44 6 The complex motor effects of MDMA are dependent on monoamine release followed by activation of multiple postsynaptic 5-HT and DA receptor subtypes in the brain,47 but the precise role of specific receptor subtypes is still under investigation. 

The dimer of the hormone-receptor complex should scrutinize an infinity of sequences before finding its FIRE. The role of the hormone in the recognition of the HRE seems to be that of dramatically increasing the velocity of DNA sequence recognition, that is to say, it binds and disconnects more quickly to sequences of nonspecific DNA. When it finds the sequence of its HRE, a bond of affinity is formed that is similar to that of hormone-receptor interaction (Kd in the nM range). 

The physiological hormone for the RARs is all-frans-retinoic acid RA 221 and that for the RXRs is its geometric isomer, 9-czs-retinoic acid (9-czs-RA 222) [320]. However, these polyolefinic hormones are of only limited use in elucidating the precise biological roles of each receptor family. Synthetic ligands that specifically activate only the RXR or RAR hormonal pathway and which cannot be converted into forms that activate the other pathway would be of much greater use in this regard. 

In contrast, steroid hormones, thyroxine, and retinoids bind to internal receptors. In 1968, Gorski et al and Jensen et a/.10 11 proposed independently that steroid hormone receptors in the cytoplasm bind incoming steroid molecules and after an "activation" step carry the hormone into the nucleus, where the hormone-receptor complex would bind at many sites in the chromatin inducing transcription of selected genes.12 Doubt has been cast on the assumption that the steroid hormone receptors must bind hormone initially in the cytoplasm. However, the role of steroid receptors in regulating transcription is well established (see discussion in Chapter 22, Section E,5 Chapter 28, Section C,6). 

When studying the role of various H3 receptor compounds on pituitary hormone secretion some points have to be considered a) are the actions of the compounds related to H3 receptor binding or to a non-specific action, b) are the actions related to an auto- or heteroreceptor or eventually postsynaptic receptor effect of the compounds, and c) are the actions related to an effect known to involve histaminergic neurons. In the following, we will give a short description of the effect of HA in the neuroendocrine regulation of pituitary hormone secretion (Table 1) and focus on the role of H3 receptors in modulation of the secretion of the individual pituitary hormones based on previously published investigations and our own recent experiments. 

Kulinsky, V.I. and Olkhovsky, LA. (1992). Two alternative strategies - resistance and tolerance - developing under unfavourable conditions. Role of hormones and receptors (In Russian). Uspekhi Sovremennoy Biologii 112,697-714. 

With the availability of labeled hormones of high specific activity and the application of the principles of affinity chromatography, researchers were able to isolate cellular proteins that bind to plant hormones in vitro. Such proteins have been referred to as receptor proteins, binding proteins, or acceptor proteins. Tacit in the concept of hormone receptor proteins is the stereo-specific interaction of the hormone and the receptor protein (19). The resulting hormone-protein complex participates in growth processes that depend on new or enhanced protein synthesis. Advances in molecular biology and related sciences have enabled many researchers to study the role of receptors in the control of nuclear functions or other activities and to determine the site of primary hormonal action. 

In understanding the role of different receptors in the prostate, it is essential to comprehend the role of their ligands on the prostate. Prostatic growth are controlled by endocrine factors, neuroendocrine factors, paracrine factors, autocrine factors, extracellular matrix factors, and cell-cell interactions. Endocrine factors are produced in distant organs and reach the prostate via serum transport and include steroid hormones such as testosterone and estrogen, as well as peptide hormones such as insulin and prolactin. 

VI. Vacca, A., Martinotti, S., Screpanti, 1., Maroder, M., Felli, M. P., Farina, A. R., Gismondi, A., Santoni, A., Frati, L., and Gulino, A. Transcriptional regulation of the interleukin-2 gene by glucocorticoid hormones. Role of steroid receptor and antigen-responsive 5 -flanking sequences. J. Biol. Chem. 265, 8075-8080 (1990). 

It is generally understood that in order for a compound to act via the estrogen receptor, it must be recognized by this receptor. Recognition is measured by the relative binding affinity (RBA) value of the compound for the ER, the reference value being that of estradiol (RBA = 100% by definition). It should also be noted that a second form of the receptor, ERfi, was recently discovered in various tissues and has been found in breast cancers classified as hormone-independent However, the exact role of this receptor in the cell is not yet well understood and remains a subject of debate [54, 55]. 

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