IntroductionPituitary gland hormonesFactors affecting secretionFunctionRegulation of secretionHypoprolactinaemiaHyperproltinaemiaDiagnosis and TreatmentCase StudyReferences
Human PRL is a single-chain polypeptide of 199 amino acids. It has a molecular weight of 23 kDa.
Prolactin is synthesized in and secreted from specialized cells of the anterior pituitary gland, the lactotroph cells.
The pituitary gland (also called the master gland) is an endocrine gland about the size of a pea (weighing 0.5 g) and located at the base of the brain (just below the hypothalamus).
The pituiary gland has two parts the anterior lobe and posterior lobe that have two seperate functions.
The pituitary gland secrets hormones regulating homeostasis, including tropic hormones that stimulate other endocrine glands.
Pituitary gland hormones
Hormones secreted by anterior pituitary
Hormones secreted by posteior pituitary
Factors affecting secretion
Factors increasing PRL secretion:Prolactin releasing hormone (PRH)Estrogen (during pregnancy stimulates lactotropes to secrete PRL)Oxytocin (causes muscle contractions to expel milk)Vasoactive intestinal peptide (VIP)Thyrotropin-releasing hormone (TRH)Breast feeding StressSleepDopamine antagonists (e.g. antipsychotic drugs)Chest wall traumaFactors inhibiting PRL secretion:Dopamine ( also called prolactin inhiniting hormone)Bromocryptine (Dopamine agonist)
PRL is responsible of: Primarily; initiating and sustaining lactation and stimulation of breast development along with Estrogen during pregnancy.
Other functions of PRL:
Reproductive; inhibition of ovulation by decreasing secretion of LH and FSH during pregnancy.
Regulation of immune system;by stimulating T cell functions.
Osmoregulation; transporting fluid, Na, Cl and Ca across epithelial intestinal membrane and promoting Na, K and water retention in the kidney.
Metabolism; essential in fat cell production, differentiation and regulation.
Regulation of secretion
Breast feeding is the major stimulus of prolactin production.Triggered by the prolactin releasing hormone (PRH) Inhibited by prolactin inhibiting hormone (PIH), dopamine, acting on the D2 receptors present on the lactotroph cells In males, the influence of PIH predominates.In females, PRL levels increase and decrease in accordance with estrogen blood levels;
-Low estrogen levels stimulate PIH release. -High estrogen levels promote release of PRH and thus PRL.Blood levels increase towards the end of the pregnancy.When the mother no longer needs to produce milk, dopamine inhibits prolactin by signaling the hypothalamus to stop.
Causes and Symptoms of Hypoprolactinaemia
Decreased PRL hormone secretion by the anterior pituitary glandCommon causes of Hypoprolactinaemia:Sheehan'ssyndrome (caused by ischaemic necrosis of the pituitary gland due to blood loss during or after child birth)Hypopituitarism Excess dopamine Autoimmune disease Growth hormone deficiency Head injury Infection (e.g. Tuberculosis)
Symptoms:Ovarian diseases, delayed puberty and infertility.Impotence and abnormal spermatogenesis.
Causes and symptoms of Hyperprolactinaemia
Increased PRL hormone secretion by the anteriorpiruitary gland
Common causes of HyperprolactinaemiaStress Medications e.g. Antipsychotic drugsPrimary hypothyroidim: PRL is stimulated by the increase of TRH.Pituitary gland tumoursProlactinoma: a non-cancerous tumour of the pituitary cell secreting PRL. Idiopathic hypersecretion: e.g. due to impaired secretion of dopamineOther: chest wall lesions and chronic renal failure. Symptoms:Women:OligomenorrhoeaAmenorrhoeaGalactorrhoeaInfertilityHirsutimOsteoporosis
Men (late onset):Gynaecomastia.Impotence.Osteoporosis
In both sexes, tumour mass effects may cause visual-field defects and headache.
Diagnosis and Treatment
Diagnosis:History (medications, oligomenorrhoea, hirsutim)
Physical examination ( galactorrhoea)
LaboratoryPregnancy TestProlactinMacroprolactin (inactive, large complex of serum prolactin with an IgG antibody)TSH, Free T4U&EsTes, LH, and FSH
MRI scan ( prolactinaemia)
Visual field tests (optic nerve)
Hyper prolactinaemia: dopamine agonists (e.g. Bromocriptine or Cabergoline)
Surgery removal and/or radiation therapy (large pituitary tumours)
Tyroid abnormalities: thyroid hormone replacement ( e.g. levothyroxine)
Ovarian insufficiency: hormonal therapy (e.g. Estrogens and Progestins)
A 56 years old male who was recently admitted to A&E for fall-related injuries (crackedright sided rib and right knee injury)In June, the pt was referred to the endocrine clinic due to the detection of an adrenal incidentaloma.Other clinical history include atrial fibrillation and pleural thickening.
Lab investigations (12/09/2016)
TestReference rangeResultProlactin73-407 mU/L>42000TesMale >50 yrs7-30 nmol/L3.0TSH0.35-5.0 mU/L4.64 FT49-19 pmol/L12LH2-10 IU/L2.0FSH1-5 IU/L3.0
MRI scan was performed to confirm or rule out prolactinoma.
The radiology report:46 x 37 x 35 mm pituitary tumour in keeping with pituitary macroadenoma.Encroachment of clivus, sphenoid sinus, left-sided optic pathways and cavernous sinus bilaterally.
ReferencesFreeman M. et al(2000) Prolactin:Structure, Function, and Regulation of Secretion, American Physiological Society [online] http://physrev.physiology.org/content/80/4/1523.long
Ugwa E. et al (2016) Assessment of serum prolactin levels in among infertile women with galactorrhea attending a gyneclogical clinic North-West Nigeria, Nigerian Medical Journal, [online] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924401/
Nevels R. et al (2016) Paroxetine- The Antidepressant from Hell? Probably Not, But Caution Required, Psychopharmacology Bulletin, [online] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044489/
Nessar A. (2010) Clinical Biochemistry. New York. Oxford University Press.
Besser G.and Thorner M. (1994) Clinal Endocrinology. London. Times Mirror International.