17-hydroxy-progesterone (17α-OH-P) is a steroid produced in the adrenal glands and gonads (testicles or ovaries).
It is a natural progestogen, and is increased during the third trimester of pregnancy mainly due to fetal adrenal production.
As a hormone, 17OHP also interacts with progesterone receptors.
Normal levels in children are 3-90 ng/dl, in men: 139 ng/dL (< 4.17 nmol/L) and in women: it depends on the stage of the ovarian cycle:
Follicular phase: 0.2 – 2.6 ng/ml
Luteal phase: 0.35 – 4.0 ng/dL
Postmenopause: 0.1-1.2 ng/ml
Congenital adrenal hyperplasia is a disorder that affects the adrenal glands (above the kidney).
This results in a reduced production of body hormones, including cortisol and aldosterone, because one of the necessary enzyme stages present in the adrenal glands does not work properly.
When a very low amount of cortisol is secreted, the amounts of adrenocorticotropic hormone increase, which boosts adrenal hormone synthesis, giving rise to a hyperplasia of the adrenal cortex.
In other words, adults with CAH lack an enzyme, sufficient in the adrenals, to produce the final hormones. Among the hormones that the body stops producing, or produces in low amounts, are:
Cortisol: Responsible for regulating the body’s response to disease or stress.
Mineralocorticoids: Which regulate the amount of sodium or potassium.
Testosterone: Involved in sexual functions.
Lack of cortisol results in overproduction of male sex hormones, which gives male characteristics in women at an early age.
This type of non-classical hyperplasia is more moderate, is characterized by partial insufficiency and manifests in the adolescent phase or in adults, and may even remain asymptomatic (cryptic forms).
In adult men:
Growth of beard and other hairs at an early age (early puberty).
Growth at an early age, but their final height will be short to average.
Enlargement of the penis despite having small testicles.
Low sperm production.
Infertility or sterility problems in men and women.
Unexpected mood swings.
The high amount of potassium should be monitored.
This type of CSH (non-classical) is not fatal, so life is not at risk, however, it can harm various functions of the body that will lead to a decrease in the patient’s quality of life.
If this syndrome appears in adulthood and there are no symptoms, there is no need for treatment. Only if the symptoms affect the person’s quality of life should the disease be treated.
The people most affected by this condition are women, as it causes a greater development of coarse hair, following a male pattern, in different parts of the body, in addition to causing sterility or problems for pregnancy.
The congenital adrenal hyperplasia generates a greater production of androgens (male cells) in those affected, since the adequate cortisol is not generated, in some occasions.
Therefore the treatment will be based on reducing the excessive production of these male hormones using glucocorticoids, or also, preventing the effects of androgens on receptors, using antiandrogens.
The glucocorticoid most commonly used to treat congenital adrenal hyperplasia in adults is hydrocortisone, as it has the same potency to that of endogenous cortisol.
This treatment aims to reduce the signs and consequences of hyperandrogenism such as hirsutism and sterility.
As with other steroids, 17α-OH-P is synthesized from cholesterol through a series of steps mediated by enzymes. The first step in this pathway, the conversion of cholesterol into pregnenolone, is stimulated by adrenocorticotropic hormone (ACTH) and not by gonadotropins.
Pregnenolone then becomes either progesterone or 17-hydroxypregnenolone, both compounds are precursors to 17α-OH-P.
In the adrenal glands, 17-hydroxypregnenolone can then be transformed into cortisol through the sequential actions of the enzymes 21-hydroxylase and 11-hydroxylase.
Both in the adrenal glands and in the ovaries, 17α-OH-P can also become, thanks to the action of another enzyme in androstendione, a precursor of testosterone and estradiol.
As with cortisol, serum concentrations of 17α-OH-P present under normal conditions a pattern of diurnal variation that depends on ACTH, with maximum levels in the morning and minimums in the evening.
In addition, ovarian production of 17α-OH-P increases during the luteal phase of the menstrual cycle, which leads to an increase in ovarian production than during the follicular phase.
The determination of circulating concentrations of 17α-OH-P is a standard tool in the clinical evaluation of 21-hydroxylase deficit, the most frequent cause of congenital adrenal hyperplasia (classical and non-classical form).
21-hydroxylase deficiency is an autosomal recessive disorder that appears in approximately 1:15,000 live births.
Due to the reduced activity of 21-hydroxylase, 17α-OH-P cannot be effectively converted into cortisol, but instead accumulates in large quantities and drifts into the androgen biosynthesis pathway, such as androstendione, which will also be increased, as well as DHEA and androstenediol.
Hydroxyprogesterone is the substrate for hydroxylation at position 21 in cortisol biosynthesis.
Keywords: late adrenal hyperplasia and hydroxyprogesterone, cortisol and hydroxyprogesterone, aldosterone and hydroxyprogesterone, hydroxyprogesterone and hyperandrogenism, hirsutism and hydroxyprogesterone, infertility and hydroxyprogesterone, 21_hydroxylase and hydroxyprogesterone deficit, adrenal hyperplasia, congenital and hydroxyprogesterone, androstendione and hydroxyprogesterone, precocious puberty and hydroxyprogesterone.