Receptor phosphorylation, progesterone

Tesarik, J., Moos, J., and Mendoza, C. (1993). Stimulation of protein tyrosine phosphorylation by a progesterone receptor on the cell surface of human sperm. Endocrinol. (55 328-335. 

Nakao, M., Mizutani, T Bhakta, A., Ribarac-Stepic, N. Moudgil, V.K. (1992). Phosphorylation of chicken oviduct progesterone receptor by cAMP-dependent protein kinase. Arch. Biochem. Biophys., 298, 340-8. 

Poletti, A., Conneely, O.M., McDonnell, D.P., Schrader, W.T., O Malley, B.W. WeigeL N.L. (1993). Chicken progesterone-receptor expressed in Saccharomyces caevisiae is correctly phosphorylated at all 4 ser-pro phosphorylation sites. Biochemistry, 32, 9563-9. 

In addition to PR-mediated transcriptional activities, progesterone also triggers intracellular phosphorylation cascades of the Src/Ras/mitogen-activated protein kinase pathway via PR [10, 11]. Also independent of the transcriptional activities of the receptor are rapid nongenomic effects of progesterone like modulation of sperm acrosome reaction [12], prevention of preterm labor [13] and Xenopus oocyte maturation [14]. 

Although sterols are present in most mammalian body tissues, the proportion of sterol ester to free sterol varies markedly. For example, blood plasma, especially that of Man, is rich in sterols and like most plasma lipids they are almost entirely found as components of the lipoproteins about 60-80% of this sterol is esterified. In the adrenals, too, where cholesterol is an important precursor of the steroid hormones, over 80% of the sterol is esterified. However, in brain and other nervous tissues, where cholesterol is a majof component of myelin, virtually no cholesterol esters are present. Cholesterol esters are formed by the action of a microsomal acyl-CoA cholesterol acyl transferase (AC AT) which is present in most cells. Under normal conditions the enzyme is considered rate-limiting for cholesterol esterification. It is regulated by progesterone and may be modulated by phosphorylation/dephosphorylation like HMG-CoA reductase. Under conditions where cells take up a large amount of cholesterol, such as via LDL receptors, ACAT is induced. The enzyme is particularly important in intestine and is relatively low in liver where the lipoproteins made for secretion into the serum contain little if any cholesterol ester. 

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