Progesterone interactions with steroid receptors

Small lipophilic (lipid-soluble) hormones diffuse across the plasma membrane and then interact with intracellular receptors in the cytosol or nucleus. The resulting hormone-receptor complex often binds to regions of the DNA and affects the transcription of certain genes (see Topic G7). Small lipophilic hormones with intracellular receptors include the steroid hormones which are synthesized from cholesterol (see Topic K5) (e.g. the female sex hormones estrogen and progesterone), thyroxine which is produced by thyroid cells and is the principal iodinated compound in animals, retinoic acid which is derived from vitamin A, and vitamin D which is synthesized in the skin in response to sunlight (see Topic K5). 

Steroids are a class of lipids characterized by a sterane core and additional functional groups. Hundreds of distinct steroids are found in plants, animals, and fungi. It is possible to classify steroids based on their chemical composition into cholestanes (e.g., cholesterol), cholanes (e.g., cholic acid), pregnanes (e.g., progesterone), and androstanes (e.g., testosterone and androgen). Steroids play many important biological roles, often as hormones interacting with specific receptors. The hydrophobic... 

There are now indications for the interaction of progesterone metabolites with the Cl channel of the GABAa receptor (Fig. 52-7). The A-ring-reduced steroids, especially those with the 5a,3a configuration, are particularly active on the GABAa receptor [ 12]. By facilitating chloride-channel opening, these steroids produce anesthetic, anxiolytic and sedative-hypnotic effects (see Ch. 16). 

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

The interaction of CSN5 to the member of the IkB multigene family Bcl3, the progesterone receptor PR, and the steroid receptor co-activator SRC-1, leads to stabilization of Bcl3-p50 and PR-SRC-1 complexes and enhances transcriptional activity [42, 43]. Whereas AP-1 activity is stimulated by interaction of CSN5 with the integrin adhesion receptor LFA-1 [44], the opposite effect was reported in the... 

But how do these ovarian and testicular hormones exert their effects All cells that interact with these steroid hormones have receptors for them within the cytoplasm. The presence of oestrogen receptors was first demonstrated by Jensen and Jacobsen in 1962. The hormones pass through the cell membrane and then encounter receptors that are specific for each of the classes of hormones the oestrogens, androgens, progesterone and glucocorticoids... 

Not only do oocytes take up progesterone from the medium, but also they appear to retain a substantial proportion of the hormone (about 50%) for prolonged periods of time when incubated in hormone-free medium (Smith and Ecker, 1971). This bound steroid fraction was not competed out by the presence of a 100-fold excess of unlabeled progesterone. However, the additional observation that intracellular hormone could be coprecipitated with a protein extract (Smith and Ecker, 1971 see also Horton, 1969) led to the idea that this intracellular hormone might be responsible for the initiation of maturational events, possibly through interaction with a specific protein receptor. This appears not to be the case. 

Edwards DP, Wardell SE, Boonyaratanakornkit V (2002) Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways. J Steroid Biochem Mol Biol 83 173... 

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