Hyperprolactinaemia, as the cause of miscarriage

Prolactin has a structural similarity with the growth hormone, is a polypeptide, is formed in the pituitary gland. In 1981, cloning of the prolactin gene was carried out. It is believed that it is formed from a common somatomamotropic precursor. The prolactin gene is located on the 6th chromosome. Synthesis and secretion of prolactin is carried out by the lactotrophs of the adenohypophysis and is under the direct control of the hypothalamus. The hypothalamic-pituitary system has both a retarding and stimulating effect on the secretion of prolactin through neuroendocrine, autocrine and paracrine mechanisms.

Several forms of circulating prolactin are described:

1. "Small" prolactin (MM-22000) with high activity;
2. "Large" prolactin (MM-50000) and
3. "Big big".

"Large" prolactin and "big-large" have a low affinity for the receptors. It is believed that fertility is maintained by the "large-large" prolactin, which in plasma can turn into a "small". The main prolactin-inhibiting factors are dopamine (DA), y-aminobutyric acid (GABA). In the regulation of prolactin secretion, tirotropin-releasing hormone, serotonin, opioid peptides, histamine, oxytocin, angiotensin, etc. Participate. The secretion of prolactin in physiological conditions is caused by sleep, eating, exercise, stress. In pregnant women, the level of prolactin begins to increase in the first trimester of pregnancy and increases to its end, exceeding by 10 times the level of prolactin before pregnancy. It is believed that this increase is due to an elevated level of estrogen.

In the fetus, prolactin begins to be produced at 12 weeks with a rapid increase in the last weeks before childbirth. By the end of pregnancy, the level of prolactin in the fetus is higher than that of the mother, but after childbirth, it quickly declines by the end of the first week of life. Prolactin is found in the amniotic fluid in an amount 5-10 times higher than its level in the plasma. The maximum amount of prolactin is noted in the II trimester of pregnancy.

Prolactin can synthesize the chorion and decidual membranes. Moreover, dopamine does not affect the synthesis of prolactin with decidual tissue. It is suggested that prolactin, produced by decidual tissue, takes part in osmoregulation of the amniotic fluid and, together with decidual relaxin regulates uterine contractility.

With miscarriage, no serious disorders of prolactin synthesis are associated, as is observed with infertility. In patients with miscarriage, the prolactin level is elevated insignificantly and does not cause gallectorea and / or amenorrhea, but it significantly disrupts the menstrual cycle due to the androgenic effect of prolactin excess. According to the researchers, in 40% of patients with hyperprolactinemia there is a violation of the secretion and metabolism of androgens. In such patients, the level of DEA and DEA-C was increased. The level of globulin binding steroids is also reduced by the action of prolactin on the liver.

Clinical signs of hyperandrogenism, as a rule, are absent, this is due to the increase in less active androgens. An increase in free testosterone and androstenedione is noted only in some women. The level of free dehydrotestosterone in such patients is reduced by reducing the activity of 5a-reductase (the enzyme responsible for the action of androgens on the hair follicle) under the action of prolactin. Elevated levels of prolactin are often combined with hyperinsulinemia and may be important in the development of insulin resistance. It is believed that hyperprolactinemia can disrupt the normal function of the ovaries. A high level of prolactin in the early follicular phase inhibits the secretion of progesterone, and a lower level of prolactin in mature follicles contributes to increased secretion of progesterone.

According to many researchers, in the case of hyperprolactinemia, infertility is observed precisely because of its effect on steroidogenesis and an excess of androgens, but if the pregnancy has occurred, then its course usually proceeds without significant complications.

[1], [2], [3], [4], [5]