ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 ME9

Prolactin: an underestimated hormone

Sevim Gullu

Department of Endocrinology and Metabolic Diseases, Faculty of Medicine, Ankara University, Ankara, Turkey.

Prolactin (PRL) is a peptide hormone and secreted by the lactotrophs in the anterior pituitary gland. Its secretion is regulated by the hypothalamus and under control of inhibitory effect of mainly dopamin. Gamma-aminobutyric acid (GABA) and other unidentified prolactin-release-inhibiting factors has also effects on PRL secretion. Thyrotropin-releasing hormone (TRH) is a prolactin-releasing factor. Vasoactive intestinal peptide (VIP), oxytocin and galanin are the other probable prolactin-releasing-factors.

Human PRL is a single-chain polypeptide of 199 amino acids. It has a molecular weight of 23 kDa but several variants of PRL exist.

Besides its main lactogenic action it is now known that, from animal studies, has several other actions including osmoregulation, reproduction, behaviour modification and immune modulation. In animal models tumour-promoting role of locally produced PRL PRL in breast and prostate has been established. Local production of PRL in breast and prostate tissues in human has also been demonstrated but its role in tumourogenesis is not known. It has been suggested that increased PRL level is a risk factor for human breast and probably prostate cancer but more data is needed to prove this.

PRL is proposed as a metabolic hormone as well. PRL is locally secreted from adipose tissue. PRL excess results in increased food intake and body weight in animal models. Recent data indicate that PRL has a role in insulin sensitivity. PRL stimulates insulin release and regulates adipokine secretion. A role of prolactin in obesity related complications has also been suggested.

Immunoregulatory effects of PRL have also been extensively studied. PRL is secreted by lymphocytes. There is evidence that PRL has acute and chronic effects on immune and autoimmune responses. In animal models of rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and uveitis suppression of prolactin by bromocriptine improves disease outcome. There are several studies in which bromocriptine has been demonstrated to suppress autoimmune responses in rheumatic and autoimmune diseases.

Hyperprolactinemia refers to an increase in circulating levels of PRL and is the most common pituitary hormonal abnormality. There are several causes of hyperprolactinemia. Hypothalamic lesions such as tumours and inflammatory processes and drugs such as alpha-methyldopa diminishes dopamin secretion and may cause hyperprolactinemia. Lesions of the pituitary stalk, such as stalk tumors and inflammation, may also cause hyperprolactinemia due to impaired dopamin transport to lactotrophs. Drugs that act as dopamin-receptor-blocking agents such as chlorpromazine, haloperidol, metoclopramide, sulpiride and domperidon block the effects of dopamin and give rise to hyperprolactinemia. Hypothyroidism, estrogens, chest wall lesions are other causes of hyperprolactinemia. Prolactinomas are the PRL secreting tumours of the pituitary gland and cause hyperprolactinemia. These are the most common type of hormone secreting pituitary tumors and the most common cause of tumoral hyperprolactinemia.

Clinical manifestations of hyperprolactinemia are galactorrhea and hypogonadism. Signs and symptoms of the causing disorder and manifestaions of other hormonal dysregulations may also be found in patients. Menstruel abnormalities-amenorrhea or oligomenorrhea- are usually seen in hyperprolactinemic women. Infertility is another manifestation in both genders. Decrease in bone mineral dansity as a result of estrogen deficiency can also be seen. Puberty may be delayed in adolescents. Gynaecomasty and galactorrhea are rarely seen in men.

Differential diagnosis of hyperprolactinemia is very important for clinicians. The most common reasons in clinical practice are pharmacotherapeutic agents. It should be kept in mind that mild stress, even the stress of venepuncture, can induce transient elevations in serum PRL. Initial assessment of a patient with hyperprolactinemia should include medical and drug history and careful physical examination. Serum prolactin levels are ideally measured in the morning in a fasting state. Prolactin levels should not be measured after an examination since the stress of a gynaecological or breast examination may raise the prolactin levels. Biochemical assessment should include beta-hCG, renal and liver function tests, thyroid functions. If serum PRL level is mildly elevated the test should be repeated before further evaluation. Since hyperprolactinemia can be seen in patients with PCOD this should be ruled out in patients presenting with oligo-amenorrhoea. PRL may form immune complexes and may produce ‘macroprolactin’. Since this molecule is biologically inactive but can be detected by the PRL assays, this possibility should be kept in mind especially if the patient has no apparent hyperprolactinemic symptoms. Polyethylene glycol precipitation is the method of choice to confirm macroprolactinaemia. In patients with clinical signs and symptoms of hyperprolactinaemia and normal serum prolactin levels, the high-dose hook effect needs to be considered.

Magnetic resonance (MR) imaging of the sellar region should be performed in patients with persistently elevated PRL levels.

The objectives of treatment of hyperprolactinaemia are to normalize serum PRL levels and resolve clinical manifestations. Indications for treatment are: macroprolactinoma, patients with menstrual irregularities, infertility, tumoural compression symptoms and low estrogen levels. Treatment options are pharmacotherapy, surgery and irradiation. Asymptomatic patients may not be treated but should be observed periodically.

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