Prolactin is a peptide hormone synthesized in lactotroph cells constituting about 20% of the anterior pituitary gland. PRL secretion is pulsatile and exhibits a circadian rhythm, with the highest concentrations during sleep and the lowest in the morning, about 2–3 hours after waking up. Peak serum PRL levels are observed between 4 and 6 am. PRL has a half- life of about 50 minutes and is mainly metabolized in the liver and, to a lesser extent, in the kidney.

Serum PRL levels transiently increase following exercise, meals, sexual intercourse, minor surgery, general anesthesia, acute myocardial infarction, and other forms of acute stress. PRL represents a stress-related hormone. In addition, during the last two trimesters of pregnancy and the first months of lactation, marked hyperplasia of lactotroph cells occurs transiently, with hypersecretion of PRL; the sucking reflex induces an increase in PRL that lasts 30–45 minutes.

PRL is the only adenohypophysis hormone undergoing dopamine-mediated inhibitory neuroendocrine regulation. Thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP), estradiol, oxytocin, and vasopressin, on the other hand, stimulate PRL release.

The PRL exerts its action mainly at the breast level, stimulating breast tissue development and promoting lactation. During pregnancy, in synergy with estrogen, progesterone, and placental lactogen, PRL stimulates further development of breast tissue aimed at milk production. After childbirth, the milk production process begins with the sudden fall of placental estrogen and progesterone, which antagonize the effects of PRL on lactation. PRL, in fact, stimulates the syn thesis of milk proteins (lactalbumin), lipids, and carbohydrates that are poured into the alveoli and mammary ducts. Nipple sucking activates a nervous reflex, which, by stimulating the secretion of oxytocin from the neurohypophysis and PRL from the adenohypophysis, maintains the lactation process. Prolactin also plays an essential role in reproductive processes through direct and indirect mechanisms. In particular, it inhibits reproductive capacity indirectly by sup pressing the synthesis and secretion of Gonadotropin-Releasing Hormone (GnRH) at the hypothalamic level, followed by a reduction in the secretion of gonadotropins and testosterone; directly, by reducing the sensitivity of LH and FSH receptors in the gonads. In this way, a state of anovulation (infertility) contributes to maintaining lactation, preventing it from being interrupted by a subsequent pregnancy. Prolactin also has a luteolytic effect, inducing a shortened or inadequate luteal phase of the menstrual cycle.

PRL exerts its biological effects through interaction with a receptor that belongs to the type 1 cytokine receptor family, to which GH and IL-6 receptors also belong.

Hyperprolactinemia

The term hyperprolactinemia refers to increased circulating PRL levels due to hormonal hypersecretion by the pituitary gland, generally associated with reproductive problems in both men and women. Hyperprolactinemia is found in physiological and pathological conditions (Table 1); according to the etiology, it can be classified into organic and functional. The most common cause of functional hyperprolactinemia is the intake of pharmacotherapeutic agents that reduce hypothalamic dopamine secretion or its inhibitory action on the pituitary gland (antipsychotics and antidepressants). Functional hyperprolactinemia is also common in pregnancy and chronic renal insufficiency due to reduced peripheral PRL clearance, polycystic ovary syndrome due to hyperestrogenism, or primary hypothyroidism due to increased TRH secretion. Organic hyperprolactinemia is, instead, due to lesions of the hypothalamic-pituitary region that compromise dopamine synthesis, its transport through portal vessels, or the response of lactotrophs elements; among these, the most common causes are pituitary adeno mas (prolactinoma and GH/PRL and ACTH/PRL-secreting adenoma), hypothalamic tumors, and infiltrative conditions (sarcoidosis, craniopharyngioma, pituitary metastases, vascular malformations, empty saddle).

Table1. Causes of hyperprolactinemia

From a clinical point of view, the main manifestations of hyperprolactinemia are amenorrhea, galactorrhea (inappropriate secretion of milk or a lactescent liquid from the breast), and infertility in women and impotence, decreased libido, and infertility in men. The onset of symptoms in men is generally later than in women because very high PRL values are required. In the case of adenoma in both sexes, the symptoms due to the expansive lesion (headache and visual impairment) can be observed.

Prolactinoma

Prolactinoma, a prolactin-secreting pituitary adenoma, is the most frequent pituitary tumor, with a prevalence of 100 cases per million population. Depending on the diameter of the tumor, prolactinoma can be differentiate into microadenomas (1 cm in diameter), which can be locally invasive and compress adjacent structures. Generally, tumor size correlates with circulating PRL levels. Microprolactinomas are quite frequent in females and rare in males, with a male-to-female ratio of 1:20; this ratio becomes 1:1 for macroprolactinomas.

Laboratory Investigations

Blood sampling for PRL levels measuring should be per formed in the morning in a fasting patient who has been awake for at least 2 hours. Since PRL secretion is pulsatile, a single determination is not sufficient to diagnose hyperprolactinemia; at least two blood samples should be taken 30–60 minutes apart, preferably using a needle cannula because puncture of the vein can also induce an increase in PRL secretion, or three samples taken on three different days. The normal range of serum PRL levels in adults is 10–25 ng/mL in women and 10–20 ng/mL in men. In patients with very high prolactinemia (>1000 ng/mL), values may be lower due to artifacts of the assay method; in these cases, the sample should be diluted.

Diagnosis and Therapy

 Hyperprolactinemia The finding of serum PRL levels >25 ng/mL indicates hyperprolactinemia.

The treatment of hyperprolactinemia depends on the etiology. However, regardless of the cause, it aims to normalize PRL levels. Dopamine-agonist drugs are used in many forms of hyperprolactinemia. In asymptomatic patients with hyperprolactinemia, treatment is not necessary.

Prolactinoma

 Once physiologic and drug-induced hyperprolactinemia is excluded, the diagnostic suspicion of prolactinoma is raised for PRL values >100 ng/mL; PRL values >500 ng/mL are diagnostic of macroprolactinoma. Once a condition of hyperprolactinemia is identified, MRI or CT scan is necessary to define the presence of a lesion compatible with a pituitary tumor.

The first choice treatment in patients with a prolactinoma is dopamine agonist therapy aimed at reducing tumor size and PRL levels. In patients with asymptomatic microprolactinoma no treatment is necessary; these patients should have regular follow-ups with serial measurements of PRL levels and MRI. Surgery is indicated in patients intolerant or unresponsive to long-term drug therapy.

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مواضيع ذات صلة

Disorders of ADH secretion and action

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thyroid-stimulating hormone (TSH, Thyrotropin, TRH stimulation test)

thyroglobulin (Tg, Thyrogen-stimulated thyroglobulin)

thrombosis indicators

Laboratory Investigations of Growth Hormone

Growth Hormone Deficiency

Laboratory Diagnosis of Thrombophilia

thromboelastography (Thromboelastometry)

throat and nose cultures

testosterone (Dihydrotestosterone [DHT])

Biomarkers of Stroke