16α-Hydroxyprogesterone (16α-OHP), also known as 16α-hydroxypregn-4-ene-3,20-dione, is a minor

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...

steroid hormone and a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

that is formed in lower amounts than

17α-hydroxyprogesterone 17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many ot ...

(17α-OHP). It occurs in

micromolar Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of ...

concentrations and its physiological relevance hence is questionable. However, it may accumulate in target tissues and could have a physiological role in the reproductive system and mammary gland development as well as the cardiovascular and central nervous systems. 16α-OHP is formed from progesterone via 16α-

hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...

primarily by CYP17A1 and primarily in steroidogenic tissues including the adrenal glands, testes, and ovaries. It is also synthesized from progesterone during pregnancy by hepatic

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzymes like

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

and CYP1A1 in the fetal liver as well as placenta. It appears to be an end metabolite of progesterone and does not seem to be further metabolized. 16α-OHP has approximately 67% and 43% of the affinity of progesterone for the

PR-A The progesterone receptor A (PR-A) is one of three known isoforms of the progesterone receptor (PR), the main biological target of the endogenous progestogen sex hormone progesterone Progesterone (P4) is an endogenous steroid and progestoge ...

and

PR-B The progesterone receptor B (PR-B) is one of three known isoforms of the progesterone receptor (PR), the main biological target of the endogenous progestogen sex hormone progesterone. The other isoforms of the PR include the PR-A The progestero ...

, respectively, and acts as an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of these receptors similarly to progesterone. It was found to produce natriuresis similar to that produced by spironolactone when administered to humans, suggesting that it also has antimineralocorticoid activity similarly to progesterone. However, surprisingly, 16α-OHP showed low affinity for the mineralocorticoid receptor (MR) of greater than 1 μM (compared to 1 nM for progesterone) and showed no

antagonism Antagonism may refer to: *The characteristic of an antagonist *Antagonism (chemistry), where the involvement of multiple agents reduces their overall effect *Receptor antagonist or pharmacological antagonist, a substance that binds to the site an ...

of the MR at up to a concentration of 1 μM (whereas progesterone shows potent such activity). However, the findings of another study suggested that 16α-OHP antagonizes the effects of

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...

via the MR, and it may still be possible that 16α-OHP has significant antimineralocorticoid activity in some cells in spite of its weak MR affinity.

References

Antimineralocorticoids Diketones Pregnanes Progestogens Steroid hormones {{steroid-stub

See also

References