Hormonal Statins

The releasing hormones (liberins 60)) and the release-inhibiting hormones (statins) which stimulate the anterior pituitary into hormone production or inhibit release, are low-molecular peptides in comparison with the anterior pituitary hormones and are present in certain areas of the hypothalamus. The hypothalamus exerts an influence on many vital physiological processes in the organism. 

The statins have been demonstrated to markedly lower plasma LDL levels (and triglyceride levels to a lesser extent). In fact, statins were approved by the US FDA on the basis of a surrogate endpoint reduction in plasma cholesterol levels. Since we know that increased plasma cholesterol levels are correlated with increased risk of coronary artery disease, it seems logical that reducing plasma cholesterol levels would lead to reduced risk. That turns out to be true in this case. However, see the case of hormone replacement therapy (HRT) for women for a more complex example, discussed below. 

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

Receptors can mediate the action of endogenous signalling compounds and may therefore be viewed as regulatory proteins. Such receptors are the physiological targets for neurotransmitters and hormones. Other types of receptors include enzyme proteins, transport proteins and structural proteins. For example, statins inhibit an enzyme catalysing the synthesis of cholesterol and loop diuretics inhibit an enzyme that facilitates the re-uptake of salt in primary urine. 

Tone, Andrea, and Elizabeth Watkins, eds. Medicating Modem America Prescription Drugs in History. New York NYU Press, 2007. This history of medicine in America covers eight of the most influential and important drugs antibiotics, mood stabilizers, hormone replacement therapy, oral contraceptives, tranquilizers, stimulants, statins, and Viagra. Each chapter describes how the drugs become such an essential part of medical care and change the way Americans think about disease. 

With growing interest in the use of statins in women, the question naturally arises whether hormonal replacement could have any effect on their efficacy or safety. Data from the HERS (conducted in women with cardiac disorders) seem to have shown that there is no interaction (37). Estrogen replacement itself resulted in a significant increase in the early risk of primary events in women who did not use statins but not in statin users. Adjustment for statin use after randomization showed no adverse effect of estrogen on the efficacy of statins, in terms of either cardiovascular events or mortality. 

Substrates MTX, thyroxines, digoxin (Oatp2), bile salts, peptides, eicosanoids, statins, GSH, glucuronide and sulfate conjugates of hormones... 

Simulated annealing has also been applied to the conformational study of dipeptide models of Gly, Ala, and Asp pentaglycine and Leu-enkephalin [11] an analog of vasopressin [10] (3S, 4S)-statin [12] analogs of thyrotropin releasing hormone [13] and the C-peptide of Ribonuclease A [13]. 

Entero statin Galanin a-Melanocyte-stimulating hormone... 

Bile acid-binding resin therapy Oral administration of a bile acid-binding resin, or sequestrant (D), increases the loss of bile acids from the body by preventing their absorption by intestinal epithelial cells through the IBAT transport protein and reduces bile acids delivered to the blood (0) and then to the liver (0) by the transporter NTCR Step The lower levels of cytoplasmic bile acids reduce the amount of bile acid bound to the nuclear hormone receptor EXP (0) and its suppression (0) of the expression of cholesterol 7a-hydroxylase. The consequent increased levels of expression and activity of cholesterol 7a-hydroxylase (B) reduce the levels of intracellular cholesterol (0). As with the statin treatment, the reduced cellular cholesterol levels (EHB) increase LDLR activity, lower plasma LDL levels, and protect against atherosclerosis. [Part (a) adapted from M. S. Brown and J. L. Goldstein, 1986, Sdence 232 34.]... 

Release inhibiting hormones, release inhibiting factors, statins. 

Statins, release inhibiting factors, release inhibiting hormones, neurohormones synthesized in the small-cell region of the hypothalamus and transported via the bloodstream to the anterior pituitary. Members of the statins include melanostatin, somatostatin, and prolactostatin. They inhibit the secretion of melanotropin, somatotropin, and prolactin, respectively. Together with the corresponding liberins, the statins regulate the levels of the three pituitary hormones. 

---