Prolactin

OverviewOverview

Introduction Pituitary gland hormones Factors affecting secretion Function Regulation of secretion Hypoprolactinaemia Hyperproltinaemia Diagnosis and Treatment Case Study References

IntroductionIntroduction 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 hormonesPituitary gland hormones

Hormones secreted by anterior pituitary

Hormones secreted by posteior pituitary

Factors affecting secretionFactors 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 Stress Sleep Dopamine antagonists (e.g. antipsychotic

drugs) Chest wall trauma

Factors inhibiting PRL secretion:• Dopamine ( also called prolactin inhiniting

hormone)• Bromocryptine (Dopamine agonist)

FunctionFunction

o PRL is responsible of: Primarily; initiating and sustaining lactation and stimulation of breast development along with

Estrogen during pregnancy.

o 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

o Breast feeding is the major stimulus of prolactin production.

o Triggered by the prolactin releasing hormone (PRH)

o 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.

o Blood levels increase towards the end of the pregnancy.

o When the mother no longer needs to produce milk, dopamine inhibits prolactin by signaling the hypothalamus to stop.

Causes and Symptoms of HypoprolactinaemiaCauses and Symptoms of Hypoprolactinaemia

Decreased PRL hormone secretion by the anterior pituitary gland

Common causes of Hypoprolactinaemia:

o Sheehan'ssyndrome (caused by ischaemic necrosis of the pituitary gland due to blood loss during or after child birth)

o Hypopituitarism

o Excess dopamine

o Autoimmune disease

o Growth hormone deficiency

o Head injury

o Infection (e.g. Tuberculosis)

Symptoms:

o Ovarian diseases, delayed puberty and infertility.

o Impotence and abnormal spermatogenesis.

Causes and symptoms of HyperprolactinaemiaCauses and symptoms of Hyperprolactinaemia

Increased PRL hormone secretion by the anteriorpiruitary gland

Common causes of Hyperprolactinaemia Stress Medications e.g. Antipsychotic drugs Primary hypothyroidim: PRL is stimulated by

the increase of TRH. Pituitary gland tumours Prolactinoma: a non-cancerous tumour of the

pituitary cell secreting PRL. Idiopathic hypersecretion: e.g. due to impaired

secretion of dopamine Other: chest wall lesions and chronic renal

failure.

Symptoms:Women: Oligomenorrhoea Amenorrhoea Galactorrhoea Infertility Hirsutim Osteoporosis

Men (late onset): Gynaecomastia. Impotence. Osteoporosis

In both sexes, tumour mass effects may cause visual-field defects and headache.

Diagnosis and TreatmentDiagnosis and Treatment

Diagnosis:o History (medications, oligomenorrhoea,

hirsutim)

o Physical examination ( galactorrhoea)

Laboratory Pregnancy Test Prolactin Macroprolactin (inactive, large complex of

serum prolactin with an IgG antibody) TSH, Free T4 U&Es Tes, LH, and FSH

o MRI scan ( prolactinaemia)

o Visual field tests (optic nerve)

Treatment:

o Hyper prolactinaemia: dopamine agonists (e.g. Bromocriptine or Cabergoline)

o Surgery removal and/or radiation therapy (large pituitary tumours)

o Tyroid abnormalities: thyroid hormone replacement ( e.g. levothyroxine)

o Ovarian insufficiency: hormonal therapy (e.g. Estrogens and Progestins)

Case studyCase study

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)

? cause

Test Reference range

Result

Prolactin 73-407 mU/L >42000

Tes Male >50 yrs7-30 nmol/L

3.0

TSH 0.35-5.0 mU/L 4.64

FT4 9-19 pmol/L 12

LH 2-10 IU/L 2.0

FSH 1-5 IU/L 3.0

ProlactinomaProlactinomaMRI 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.”

References

Freeman 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.

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