Prolactin in the blood

Prolactin is synthesized in specialized lactogenic cells of the anterior pituitary gland; its synthesis and release are under the stimulatory-inhibitory influence of the hypothalamus. The hormone is secreted episodically. In addition to the pituitary gland, prolactin is synthesized by the decidua (which explains the presence of prolactin in the amniotic fluid) and the endometrium. Unlike gonadotropins, prolactin consists of a single peptide chain including 198 amino acid residues and has a molecular weight of approximately 22,000-23,000. The target organ for prolactin is the mammary gland, the development and differentiation of which are stimulated by this hormone. During pregnancy, the concentration of prolactin increases under the influence of increased formation of estrogen and progesterone. The stimulating effect of prolactin on the mammary gland leads to postpartum lactation.

High concentrations of prolactin have an inhibitory effect on ovarian steroidogenesis, the formation and secretion of gonadotropins by the pituitary gland. In men, its function is unknown.

Prolactin appears in the blood serum in three different forms. The predominant form is the biologically and immunologically active monomeric (small) form (approximately 80%), 5-20% is present as the biologically inactive dimeric ('large') form, and 0.5-5% is present as the tetrameric ('very large') form, which has low biological activity.

The production and secretion of prolactin by lactotropic α-cells of the anterior pituitary gland is controlled by a number of regulatory centers in the hypothalamus. Dopamine has a pronounced inhibitory effect on prolactin secretion. The release of dopamine by the hypothalamus is controlled by the nucleus dorsomedialis. In addition to dopamine, norepinephrine, acetylcholine, and γ-aminobutyric acid have an inhibitory effect on prolactin secretion. TRH and tryptophan derivatives, such as serotonin and melatonin, function as PRG and have a stimulating effect on prolactin secretion. The concentration of prolactin in the blood increases during sleep, physical exercise, hypoglycemia, lactation, pregnancy, and stress (surgery).

Reference values (norm) of prolactin concentration in blood serum

Age	Prolactin, mIU/L
Children under 10 years old	91-526
Women	61-512
Pregnancy 12 weeks	500-2000
Pregnancy 12-28 weeks	2000-6000
Pregnancy 29-40 weeks	4000-10000
Men	58-475

Hyperprolactinemia (in men and women) is one of the main causes of fertility disorders. Prolactin testing is used in clinical practice for anovulatory cycles, hyperprolactinemic amenorrhea and galactorrhea, gynecomastia and azoospermia. Prolactin is also determined when breast cancer and pituitary tumors are suspected.

When determining prolactin, it should be remembered that the detected concentration depends on the time of blood sampling, since prolactin secretion occurs episodically and is subject to a 24-hour cycle. Prolactin secretion is stimulated by breastfeeding and stress. In addition, an increase in prolactin concentrations in the blood serum is caused by a number of drugs (for example, benzodiazepines, phenothiazines), TRH and estrogens. Prolactin secretion is suppressed by dopamine derivatives (levodopa) and ergotamine.

Recently, many authors have reported the presence of macroprolactin in the blood of women with various endocrinological diseases or during pregnancy. It has also been described that there is a different ratio of serum macroprolactin ("very large" - molecular weight over 160,000) and monomeric prolactin when analyzed by different test systems. A number of test systems determine all variants of the prolactin molecule in a wide range. This circumstance can lead to different results depending on the test system used.

Blood samples with elevated prolactin levels may contain macroprolactin (prolactin-IgG complex) and oligomeric forms of the hormone. Patients with prolactin levels above reference values require differentiation of the various forms of the hormone. Macroprolactin or prolactin oligomers are determined by pre-treating a blood serum sample with 25% polyethyleneglycol (PEG-6000) and then analyzing the supernatant for prolactin. A discrepancy in prolactin levels in the treated and native samples indicates the presence of macroprolactin and/or prolactin oligomers.

The amount of macroprolactin and its oligomers is determined by calculating the ratio of prolactin concentration in the initial sample and after PEG precipitation - [(prolactin concentration after PEG precipitation×dilution)/prolactin concentration in the initial sample (before PEG precipitation)]×100%. The result of the study is assessed as follows.

• If the ratio exceeds 60%, the sample contains mainly monomeric prolactin.
• Values of 40-60% (gray zone) - the sample contains both monomeric prolactin and macroprolactin and/or prolactin oligomers. The clinician should be advised that the patient's blood should be retested (e.g., using gel filtration chromatography or another test system).
• A ratio of less than 40% indicates that the sample contains macroprolactin and/or prolactin oligomers. The result should be compared with clinical data.

To date, the clinical significance of the various forms of prolactin remains unclear.

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