The pituitary is a gland located on the so-called "sella turcica ", a sunken
site on the sphenoid bone, at the base of the brain. AND' consisting of an
anterior portion, called " adenohypophysis " and a portion posterior, called " neurohypophysis
".
In the adenohypophysis there are five different types of cells producing six
different hormones:
-lactotropic cells (PRL),
-somatotropic cells (GH),
- gonadotropic cells (LH and FSH),
-thyrotropic cells (TSH)
- corticotropic cells (ACTH).
Prolactin is a hormone produced by the pituitary gland (a gland located at the base of the brain).
Prolactin serves to promote breastfeeding in all pregnant women who have recently given birth. Practically the main function of prolactin is to stimulate the production of milk from the glandular berries of the breast. It is found in the patient who breastfeeding, in mothers, never even in the blood of women who are not in pregnancy and even in the male. In addition, the prolactivity increases and decreases its concentration, in the blood, in a short time, according to a circadian rhythm with very variable pulsatility, also on the basis of external stimuli, for example if the eyes are closed or open, if we are tired or have rested etc.
& nbsp; Lactotrope cells normally make up 15-20% of the pituitary gland and, as mentioned, they reach 70% during pregnancy, when they experience hyperplasia. In fact, with pregnancy, it is determined the increase in estrogen which stimulates the growth and replication of pituitary lactotrope cells and causes an increase in secretion prolactin. The pituitary gland doubles its size and returns to normal after the childbirth.
PRL secreted in pregnancy prepares the breasts for post-breastfeeding partum. High levels of estrogen inhibit prolactin action at the level mammary. In fact, the lactation does not occur as long as the estrogen they do not shrink after childbirth. They have many characteristics electrophysiological characteristics of neurons. The PRL gene, located on the chromosome 6, encodes a precursor that has larger dimensions than to the circulating hormone.
The main form of the fully processed hormone contains 198 amino acids (molecular weight 23000) in a single polypeptide chain containing three disulfide bridges. The forms of high prolactin molecular weight are represented by dimers, polymers, aggregates and species linked to proteins.
They may be present in small quantities in normal subjects and in larger quantities in patients with pituitary adenoma. These molecules possess a variable, but generally small, activity immunological and biological. PRL is essential for lactation. The receptors for the PRLs are members of the cytokine receptor family and are located in the breast, gonads, liver, kidney and adrenal gland.
PRL promotes the development of breast cancer in rodents; a similar correlation has not been established for human breast cancer a possible role of PRL in immune modulation. Under normal circumstances, prolactin secretion adenohypophysis is repressed by the hypothalamus.
Destroying the hypothalamus or severing the pituitary stalk increase the secretion of PRL and its blood levels. In animals, PRL secretion is required after section of the pituitary stalk the autocrine secretion of VIP by the pituitary cells. The biggest factor hypothalamic inhibitor of PRL is dopamine, but factors may also play a role inhibitory peptides such as endothelin and calcitonin. The arcuate and paraventricular nuclei hypothalamus produce dopamine; dopamine runs in the axons up to the terminals in the median eminence, where it is released (tuberoinfundibular dopaminergic system) into the portal circulation and reaches the anterior pituitary to inhibit the secretion of PRL by interaction with pituitary D2 receptors (dopamine receptors linked to adenyl cyclase).
Dopamine can play an important role in the pituitary as well rear. Intravenous administration of dopamine (2 & # 181; g / min per kg body weight) or the oral one of its precursors (e.g., L-dopa) or of agonists dopaminergics (eg, bromocriptine) inhibits the release of PRL and ultimately the proliferation of lactotropic cells and the synthesis of PRL. An increase in the PRL in the blood appears to increase hypothalamic production of dopamine, which, in its turn time, partially inhibits the release of PRL by means of a " short " feedback. & nbsp; The increased PRL during nipple sucking, in sleep, under stress and after estrogen administration seems to need a factor that stimulates its secretion, not yet definitively identified.
Although TRH is a powerful stimulator of PRL secretion, TSH (cf. The thyroid function) PRLs are independently controlled in most circumstances; breastfeeding does not cause an increase in TSH and hypothyroidism primary can & # 242; or not cause an excess of PRL. Serotonin antagonists, like methysergide, they inhibit the increase in PRL induced by sucking and by estrogen, but secretion at rest is independent of serotonin.
The antagonists of opiates, such as naloxone, inhibit PRL-induced release of PRL stress, from sucking and administering estrogen, suggesting a possible role of endogenous opioids, while morphine stimulates the secretion of PRL. However, basal PRL secretion is not affected by opioid antagonists. A sudden increase in PRL is observed within one hour of delivery in subjects normal and in pregnant women, but not in patients with prolactinoma. The mechanism it is not known.
Clinical manifestations
Excess of PRL has many causes and numerous mechanisms:
1) autonomous production (pituitary adenomas);
2) decreased dopamine or dopaminergic inhibitory action (e.g., from
hypothalamic disease or from the use of anti-dopaminergic drugs);
3) stimuli that override normal dopaminergic inhibition (e.g.,
estrogen, possible hypothyroidism);
4) decreased clearance of PRL (renal insufficiency).
- Physiological states
-Pregnancy
-Puerperium (initial period)
-Stress "
- I sleep
- Nipple stimulation
- ingestion of food
Dopaminergic receptor antagonists, Phenothiazines, Butyrophenones, Thioxanthenes, Metoclopramicle, Suipiride, Respiradone, Depleting drugs of dopamine, methyldopa, reserpina, estrogen hormones, antiandrogens, opiates Verapamil
Pituitary tumors, Prolactinomas, GH secretion adenomas e
prolactin, ACTH-secreting adenomas and prolactin (Nelson's syndrome and Cushing's disease)
Nonfunctioning chromophobic adenomas with pedicle compression
Hypothalamic and pituitary peduncle diseases
Granulomatous diseases (especially sarcoidosis)
Craniopharyngiomas and other tumors
Cranial radiotherapy
Section of the peduncle
Empty saddle
Vascular anomalies including aneurysms Lymphocytic hypophysitis
Metastatic carcinoma Primary hypothyroidism
Chronic renal failure
cirrhosis
Thoracic trauma (including surgery, herpes zoster)
Convulsions
Excess PRL (hyperprolactinemia) is associated to hypogonadism and / or galactorrhea and can represent an important symptom of adenoma pituitary or hypothalamic disease. Hyperprolactinemia is found in 10-40% of amenorrhoeic women and about 30% of cases of amenorrhea and galactorrhea is caused from PRL-secreting pituitary adenomas. Hypogonadism associated with hyperprolactinemia appears to be due to inhibition of the hypothalamic LHRH, resulting in a decrease of LH and FSH.
This functional hypogonadism can be considered, in part, as a desirable physiological mechanism, given that breastfeeding causes a decreased fertility and delays the restoration of menstruation.
Generally, the higher the prolactinaemia, the more likely an estrogen deficiency is and, therefore, amenorrhea. A wide variability of clinical manifestations, despite levels similar to hyperprolactinemia, is probably due to a different biological activity of abnormal forms of PRL produced by tumors. Hyperprolactinernia in women can cause either menstrual changes or infertility despite the presence of menstrual skies regular, due at least in part to a shortening of the luteal phase. Excess of PRL in the male can lead to reduced libido, impotence and infertility.
According to some studies, 8% of men with impotence and 5% of men with infertility have hyperprolactinaemia. With the elevation of the PRL the levels of FSH and LH in humans and serum testosterone is often low. & Nbsp; Galactorrhea (milk production outside the postpartum period) is present in 30-90% of hyperprolactinemic women.
The variations in incidence are partly due to the different accuracy with which the symptom is sought. Galactorrhea can occur without hyperprolactinerma, especially in mothers. Conversely, galactorrhea it is often an important indication of hyperprolactinaemia when associated with amenorrhea. In this condition, hyperprolactinemia is present in 75% of patients. In the male, hyperprolactinernia is a rare cause of gynecomastia or galactorrhea. & nbsp;
The PRL levels are slightly higher in women (& lt; 20 & # 181; g / l) and in men (& lt; 15 & # 181; g / l). Concentration in pregnancy of PRL begins to rise during the second quarter and peaks at the moment of childbirth; the maximum values are between 100 and 300 & # 181; g / l, generally less than 200 & # 181; g / l. The pregnancy test is essential in all patients with hyperprolactinaemia and amenorrhea, as in the case of amenorrhea alone.
Average PRL levels decrease in post partum, but they go back to each feeding. Prolactinemia over many months basal and stimulated by suction decreases. Basal levels are 4-6 months after delivery of prolactin are normal and are no longer stimulated by sucking, despite continuing breastfeeding. 1 PRL levels rise within one hour of food intake e after a seizure. & nbsp;
Hyperprolactinemic patients require careful attention drug history. Drugs that block the action of dopamine (e.g., phenothiazines, butyrophenones, metoclopramide, respiridone) and drugs that deplete stocks of dopamine (eg, methyldopa and reserpine) cause hyperprolactinaemia. Chronic cocaine abuse results in modest hyperprolactinemia. The levels of prolactin induced by these substances, provided that there is no renal insufficiency, are generally below 100 & # 181; g / l (with the notable exception of risperidone); however, concentrations above 275 & # 181; g / l have also been reported. Also if high doses of estrogen cause hyperprolactinaemia, oral contraceptives a low doses of estrogen have no such effect. In case of renal insufficiency advanced hyperprolactinemia is present in 70-90% of women and in 25-60% of men. It contributes to the development of hypogonadism in some patients with insufficiency renal.
Hyperprolactinernia in these cases can be due to both a decrease clearance and increased secretion. The cause has not yet been clarified of the hyperprolactinemia that is observed in case of cirrhosis. Severe primary hypothyroidism can result in moderate hyperprolatfinernia, both due to an increase in TRH and a decrease in doparninergic tone. As a hypothyroidism primitive can also determine an enlargement of the sella turcica, by simulating a pituitary adenorna, in all hyperprolactinemic patients it is necessary to perform thyroid function tests. In rare cases a primitive hypoadrenalism determines a reversible hyperprolactinemia.
The prevalence of hyperprolactinernia (with prolactin values higher than 75 & # 181; g / l) among 10,000 " normal " adult subjects that worked in the same factory in Japan was 0.4%. They were identified various causes. Once pregnancy, postpartum, cirrhosis, drugs, Hypothyroidism, classification, epilepsy and kidney failure, you can & # 242; attribute hyperprolactinernia to a hypothalamic or pituitary disease. Very rarely, secreting tumors are found Non-pituitary PRLs. Diseases of the hypothalamic and pituitary stalk are the cause of moderate hyperprolactinaemia (typically less than 150 & # 181; g / l). 1 hypothalamic tumors are associated with hyperprolactinernia in 20-50% of cases. & nbsp; Pituitary adenomas PRL secretions (prolactinorns) have been classified, based on their size, in microadenomas & nbsp; & lt; 10 mm) and in macroadenomas ( & gt; 10 mm). Even adenomas large, non-functioning pituitary glands can cause mild hyperprolactinaemia by compression of the peduncle and consequent obstacle to the passage of doparnine towards the gland. Some acromegalic patients (25-45%), some patients with the syndrome Nelson's disease and, rarely, patients with Cushing's disease have serum levels elevated PRL caused either by the co-secretion of the hormone by the tumor or by the pedicle compression.
Endocrinology