SITES OF SECRETION

ANTERIOR PITUITARY
Prolactin is secreted from the lactotrophs of the anterior pituitary

SITES
Extra pit sites :
ovaries :f.fluid breast Endometrium,decidua myoma renal ,lung tumours

PRL,FOLLICULAR FLUID
Similar to bld level in follicular phase,then decreases

near ovulation But in anovulatory infertility and LPD ,PRL level increases

ACTION
Primary function is initiation,maintenance of lactation
PRL is essential for E synthesis in granulosa cells

ROLE OF P. IN PREGNANCY
During pregnancy PRL is involved in surfactant

synthesis in fetal lung Prevents immunological rejection by suppressing maternal immune response Osmoregulator function preventing fetal dehydration(premenstual tension) Modulates PG mediated uterine contractility

ROLE IN POSTNATAL
Primary function is initiation,maintenance of lactation
Prolactin in breast milk plays important role for immunological function in the newborn

structure
Single chain polypeptide of 199 aa encoded by a single gene on chromosome no 6 Variants LITTLE PRL (monomer) proteolytic deletion of a a (clinical assay) BIG PRL: (dimer)failure to remove introns )BIG BIG PRL: (multimeric) molecules bind to each other(MACROPRILACTIN(not physiological active

activity
BIOACTIVITY :local action(galactorrhoea)
IMMUNOACTIVITY : ciro levels Immunoassays do t always reflect biologic situation so normal prolactin, galactorrhoea

levels
5-27 ng/ml Diurenal variations Increases in afternoon Increases I hr after sleep,reachs peak at 5-7 am decreases to nadir at morning(time of assay) Secreated in pulsatile manner 14 pulse/24 hr in follicular phase,9 pulse/ 24 hr in luteal phase

secretion
Pit I factor transcription factor is important for

activation of prolactin gene on chromosome No 6

Many hormones,neurotransmitters affect PRL gene

SECRETION CONTROL
PROLACTIN INHIBITING FACTOR(PIF):
It is a

dopamine secreted in the basal

hypothalamus into the portal circulation to supress prolactin Suckling supresses dopamine

DOPAMINE RECEPTORS
FIVE RECEPTORS DIVIDED INTO 2 GROUPS: D1 ,D2 RECEPTORS CELLS IN THE ANT PIT EXPRESS TYPE 2 RECEPTORS(D2) D2 SPECIFIC LIGAND IS CABERGOLINE,WHEREAS PROMOCRIPTINE IS A NON SPECIFIC MOST SIDE EFFECTS COME FROM ++ OF D1 RECEPTORS

SECRETION CONTROL
Other inhibitory factors:
Gama aminobuteric acid( GABA) Somatostatine Pyroglutamic acid

SECRETION CONTROL
PRL RELEASING FACTOR:
MOSTLY TRH IN SURAPHYSIOLOGIC LEVELS

SECRETION CONTROL
OTHER RELEASING FCTORS
BETA ENDORPHINES - ACETYLCHOLINE 17 B ESTRADIOL HISTAMINE SEROTONIN GONADOTROPIN-RH VASOPRESSIN VASOACTIVE INTESTINAL

- ENDOGENOUS OPIOIDS

PEPTIDE(VIP)

ESTROGEN AND PROLACTIN

ESTROGEN INCREASES PROLACTIN
PROLACTIN DECREASES ESTROGEN

ESTROGEN INCREASES PRL

E interacts with pit 1 ++ PRL
E supresses dopamine ++ PRL E ++ PRF

PRL SUPRESSES ESTROGEN

PROLACTIN --- Gn R F
PROLACTIN +++ DOPAMINE ----Gn R F

--- ---- FSH,LH ---- E PROLACTIN IN HIGH LEVEL DECREASES FSH BINDING TO GRANULOSA CELLS --- ESRTOGEN AT OVARIAN LEVEL

E,PRL
HYPERPROLACTINEMIA ---HYPOESTRINEMIA
amenorrhoea,oligo, cc resistance, osteoporosis so adding e therapy is important to act,,

CAUSES OF HYPERPROLACTINEMIA
PHYSIOLOGIC: pregnancy 200 ng/ml Lactation 300 ng/ml Sleep Stress Intercourse

CAUSES OF HYPERPROLACTINEMIA
PHYSIOLOGIC Nipple stimulation Post partum(non nursing 7 d) Suckling Newborns Anaethesia Chest wall surgery , burns,herpes, scar

CAUSES OF HYPERPROLACTINEMIA
HYPOTHYROIDISM

HYPOTHYROIDISM
HYPOTHYROIDISM ++++ TRH +++++ PROLACTIN++++ DOPAMINE ------GnRH---FSH,LH----- OVULATION

CAUSES OF HYPERPROLACTINEMIA
HYPOTHALAMIC DISORDERS: Arachnoid cyst Dermoid cyst Suprasellar cysts Cystic glioma Pineal tumours T.b. sarcoidosis

CAUSES OF HYPERPROLACTINEMIA
PITUITARY DISORDERS:
ADENOMA : MACROADENOMA(>10 mm), MICROADENOMA(<10mm) T.B. , SARCOIDOSIS

CAUSES OF HYPERPROLACTINEMIA
METABOLIC:
ECTOPIC PRODUCTION:

hypernephroma,bronchogenic carcinoma HEPATIC CIRRHOSIS RENAL FAILURE

CAUSES OF HYPERPROLACTINEMIA
DRUGS: Estrogen therapy Alpha methyl dopa(ALDOMET) RESERPINE Dopamine antagonists( phenithiazines ,metaclopramid (PRIMPERAN), dompridon(MOTILIUM) H2 receptor blockers rantidine,cemetidine Antidepresssant drugs imipramine opiates

CLINICAL PROBLEMS WITH HYPERPROLACTINEMIA

Galactorroea Amenorrhoea Galactoroea amenorrhoea Delayed puberty Anovulation,oligo-ovulation LPD

CLINICAL PROBLEMS WITH HYPERPROLACTINEMIA

Infertility
Hypoestrogenic state(osteoporosis,dry vagina, dyspareunia, small
uterus,cc resistance,-ve withdrawal bleeding)

Hypothyroidism Hirsutism PCO Neurological manifestations(adenoma) Premenstual tension Male hypogonadism,dereased lipido,potency

PROLACTINEMIA,NO GALACTORRHOEA
33% only have galactorrhoea why?
Immunoreactive ,not bioactive Inadequate E,P primming of breast

GALACTORRHOEA,NO PROLACTINEMIA
50% only have normal PRL why?
Transient episode of prolactin Sensitive breast tissues Bioactive not immunoreactive PRL

Amenorrhoea , galactorrhoea
Amenorrhoea,galactorrhoea 2/3 have

hyperprolactinemia
Amenorrhoea,galactorrhoea,hyper PRL --- 1/3 have

adenoma

MANAGEMENT
DIAGNOSIS,HISTORY,EX ,CLINICAL STATE INVESTIGATIONS: PROLACTIN ASSAY TSH INCREASE T3,T4 DECREASE MRI POLYTOMOGRAPHY FOR PIT

MANAGEMENT
DOPAMINE AGONIST
ELTROXINE E REPLACEMENT THERAPY,(HRT),PILLS SURGERY

DOPAMINE AGONISTS
BROMOCRIPTINE

2.5 mg PARLODEL LISSURIDE 0.2 mg DOPERGINE PERGOLIDE 75 ug NORPROLAC Cabergoline 0.5 mg DOSTINEX

HYPOTHYROIDISM
ELTROXINE

HRT
HYPOESTROGENIC STATE
CC RESISTANCE -VE WITHDRAWAL OSTEOPOROSIS DYSPAREUNIA

PIT ADENOMA
> 100 ng/ml PRL OR NEUROLOGICAL SIGNS MRI ,

CT, PIT BLISTERING OR EROSION OF LAMINA DURA

PITUITARY ADENOMA
MEDICAL TREATMENT IS USED IN MOST

PATIENTS REPEAT MRI 6-12 MONTH.THEN 1-4 yr

SURGERY(TRANS-SPHENOIDAL MICROSURGERY)

IF RPL REMAINS ELEVATED,OR RECURRENCE,CNS SYMPTOMS,RAPID GROWTH

Surgical Care
General indications for pituitary surgery include : 1. Patient drug intolerance, 2. Tumors resistant to medical therapy, 3. Persistent visual-field defects in spite of medical treatment, and 4. Patients with large cystic or hemorrhagic tumors. Trans-sphenoidal surgery is the conventional procedure.

Radiotherapy
Rarely needed
Radiotherapy should be considered in patients with

macroadenomas who are resistant to or intolerant to medical therapy and in whom surgery has failed or in

recurrence

ADENOMA IS NOT A CONTRAINDICATION FOR PREGNANCY OR O Cs

SALAH ABD RABBO

SALAH ABD RABBO