Prolactin

1)         Have you enough  time  to refresh your knowledge on a) synthesis of PRL molecules, b) Extra-Pituitary  sites of PRL synthesis i.e.  different sites of synthesis  , c) when and how to draw a blood sample for PRL (Prolactin) , d) when to stop the  psychotropic drugs before estimating PRL e) Biological actions of PRL both   in Women and men !!!! What is  (Hook effect) in cases of Pit adenomas?? .

Q.1:- Where PRL is synthesized?? Ans:-

Prolactin (PRL) - is

secreted from  many sites of human body !!! such as  1) ant Pituitary by Lactotrophs which  compromise about 15-25% of entire cell population of adenohypophysis. 2)  PRL is also synthesized in  some other parts of brain cells 3) from  Lymphocytes and PRL released from such sites  helps in immune functions of the body. May help Covid-19!!!

Q.2:- . How many of us are aware that PRL  Controls autocrine & paracrine functions of many cells of body ?? Ans: It like growth hormone and many other growth factors  PRL act like growth hormone . Placental PRL and Pit hPL  both control- angiogenic activities. Lastly PRL may have an etiologic role in causation of Breast Ca & prostate ca!!!  

Q.3: Who controls PRL synthesis ?? Where from signals come –“Red/Yellow/green signals”-  & how PRL is faced to  release as pulses (so not to be estimated from one sample of blood only , not to drawn after 10 am-circadian rhythm has to be considered )?? Secretion of Prolactin is under  inhibition of interpolate hypothalamus . However it is suffice  to know that its tonic secretion is controlled by PIF (Dopamine).

Oestrogen , by contrast promotes synthesis and release of PRL.  In peri-ovulatory period we should not ask her  to estimate PRL as it will be falsely high due to more oestrogens which promotes and cause release of  PRL stored at Pituitary . We know that at ovulatory period E2 is temporarily high so PRL will be falsely high.

Progesterone depresses serum PRL-(while on mini pills –never estimate PRL-to stop minipills for 6 days before one embarks on PRL assay )  Oestrogen, as mentioned  stimulates its release and in pregancy PRL may be 2000 ng/ml. -

The serum level comes down to normal after 3-4 days of stoppage of OCP .

PRL release from adenohypophysis:-maintains a Circadian Rhythm: Diurnal variation:-

Pulsatile release: In late follicular phase 14 pulses per day and in late luteal phase the total pulse per day is 9/ daily. Each pulse last for 70 minutes and with an inter-pulse interval of about 70 minutes. So dear members how relevant is to  collect blood sample  for PRL every  20 minutes and  assay is made from pooled sample , as is important to estimate PRL after first treating  the serum with polyethylene glycol which will help the big bio inactive molecules of PRL to get deposited and only the supernatant of plasma is to be assed for PRL(like sperm preparation method).

Are U a clinician/ Doctor in charge of a reputed Lab --Lab owner/ Lab Technician?? Be aware of the fact that the following factors  may cause false  rise of PRL: - Stress, Smell (Olfaction), Audition( a noise) may suddenly alter the decrease of Dopamine and there may be false rise of PRL!!!! See how fallacious is PRL report!!!! So interpret with caution.  After knowing all these basic  factors of pulsatile release  we come to the conclusion that  blood for PRL should be drawn in a calm dark room in presence of close relative with a song of her choice on  from a fixed audio set. But  her mobile should be off so also her relative mobile preferably a female technician should draw  blood –she will feel comfortable in dark room)  –so that environment is peaceful) . This is like Semen collection Room- to minimize collection  failure in  a Lab settings.  It is our duty to remember that Chr stress & exercise do not cause much rise of PRL but  breast stimulation,  Venepunture can cause slight elevations of PRL .

When to collect samples?  Ans:-Mid morning by 10 am latest like DHEASO4 , Cortisol , no physical examination on that day .

Suppose report come high: What next?  : Jumping on cabergolin??  Ans: No, Enquire whether she  is overdue as a delay of 4-5 days of expected period  much E 2 will promote PRL. . Enquire is she already pregnant: - In preg due to high rise of E2à PRL  start rising at 6-8 weeks of preg—surprisingly, What happens at Br feeding??  Regardless of breast feeding PRL comes to near normal 6 weeks after delivery and it is the suckling reflex which promotes myo epithelial cells of Lacteal ducts to eject milk.  So postpartum contraception should begin after 6 weeks as Ovulation can occasionally occur due to almost normalization of PRL .

Few words on micro & macroadenoama of Pituitary: :-Of all pituitary adenomas 30-40% if a & 10% of all other  intracranial neoplasms are prolactinoma which are essentially beningn .  There is one syndrome called “Type 1 Syndrome”- where genetic change is so that there are multiple endocrine tumours at different sites in the same person. AS mentioned, most Lactotrophs tumours are benign. If adenoma size is < 1 cm then the usual serum level is expected to be 200 ng/ml. But if size is 1 cm to 2 cm in diameter than PRL value may exceed 1000 ng/ml .Above such diameter the level can be higher still. As stead in pregancy it can be 2000- 3000 ng/ml due possibly to rise of orstrogens .

Pitfalls in the assay report in cases of Pit adenoma :-

2)         If cystic adenoma-then serum level may not correlate with the size of tumour.

3)         Artifact in the immunoradiometric assay.-if too low in a case of tumour then dilutes the sera . Then only the serum  will yield appropriate result. (Hook effect).

4)         Any disease or tumour near Hypothalamus can impede secretion of PIFà so as a result rise of PRL. Head trauma, Craniopharyngioma, infiltrative diseases if brain, Kochs, malig deposits.

5)         Hypothyroidism- Hypothyroidism per see usually do not cause rise of basal PRL. What happens is that in cases of hypothyroidism if TRH is administered as a challenge dose then PRL will rise. This effect is due to the effect of raised TRH (thyrotrophin released form hypothalamus) . MRI of Pit may be solo investigation of diagnosis  of Pit tumours.  enlargement of thyrotrophic adenoma and not Lactotrophs adenoma.

6)         Pharmacological agents causing Hyperprolactinaemia:-

7)         Resperidone, olanzapin, phenothiazine, Clomipramine, pimozide, haloperidol, & domperidone.  Then what is to  be done?? . Four days after Ry stoppage of this drugs the PRL will hopefully come out of the ill effects of the drug.. Additionally, MAO inhibitors (pargyline, clorgyline,   opiate antidepressants codeine, Desipramine, Amitryptiline, Clomipramine all can raise of PRL...

 !!! What about PRL in Males

PRL is found in high conc in semen and PRl in seminal plasma helps in Spermatozoa metabolism à Glucose oxidation, Fructose utilization, Glycolysis.