Endocrinology, lecture on Prolactin
XX. Prolactin and Growth Hormone
A. PrL, GH, and CS: a family of peptide hormones
1. significant amino acid sequence homology
a. share some biological activities
2. genetic homologies
a. between hormones... also between species
b. arose by gene duplication (variant repetition)
3. receptor homologies
B. Functional homologies
1. anabolic
a. GFs may mediate actions
XXI. PrL
A. Regulation of PrL
1. the only adenohypophysial hormone primarily under
tonic inhibitory control
a. mammotropes secrete PrL unless inhibited
2. DA is the PrL-RIH
a. DA inhibited by 5-HT
i. \ 5-HT indirectly stimulates PrL
3. PrL can also be stimulated
a. PrRP (prolactin releasing peptide), TRH stimulate
5-HT, & VIP stimulate PrL release
i. E2 stimulates 5-HT & TRH
ii. PrRP binds to GR3 receptor (7tmR)
(1) only on lactotropes
b. suckling neural reflex stimulates PrL
4. PrL released in short pulses (like GH)
a. most abundant during sleep
B. PrL-Receptor
1. found in mammary, liver, pancreas, kidney, adrenal, placenta,
ovary (granulosa and corpus luteum), testes, epididymis,
seminal vesicle, prostate, lymphocytes, choroid plexus, hypothalamus
2. three forms - long (most common) intermediate, short
cytoplasmic domain: glycoprotein, spanning the membrane once
a. similar to GH-R, Epo-R, and most IL-R
= cytokine/hematopoietin receptor family
3. up-regulated following puberty, during pregnancy
and lactation
a. up or down regulated by PrL depending on [PrL]:
ñ PrL ® ñ PrL-R
b. up or down regulated by GH depending upon pulsatile
or constant secretion of GH
C. Mechanism of action
1. PrL-R activates JaK2
a. also activated by GH, Epo, IL3 via their receptors
b. stimulates DNA synthesis, cell replication,
and gene transcription
i. PrL ® PRL-R ® JaK2 ® PRL-R ® STAT5 ®
®DNA ®mRNA ® protein
D. Function
1. over 100 - more known actions than any other hormone
2. mammary gland
a. stimulates DNA synthesis, cell proliferation,
synthesis of milk proteins, fatty acids and lactose
b. ñ milk protein gene transcription & mRNA stability
c. synergistically with E, insulin, T3, and B/F
i. may involve IGF1
ii. P inhibits milk protein mRNA accumulation and translation
d. stimulates Crop Sac secretion in pigeons and other columbiformes
i. crop milk feeds young
ii. PrL with E2 promotes brood patch development
3. osmoregulation
a. ion and water permeability in skin
b. species whose life cycle bring them into
dramatically different environments
i. anadromous (saltwater to fresh)
+ catadromous (fresh to salt) fish
ii. amphibian metamorphosis
(1) movement of adults back to water
for reproduction
4. promotes premigratory fattening and restlessness in birds
5. reproductive functions
a. mammotropic in all mammals
b. gonadotropic in rodents
i. human gonads have PrL-R
(1) hyperprolactinemia can cause
amenorrhea or impotence
c. brooding behavior in birds
d. parental behavior
5. growth
a. besides mammary hyperplasia, affects larval growth
6. metabolism
7. immune effects
a. PrL is synthesized in the immune system
b. mitogenic for immune cells
c. receptor homologies with cytokines (e.g. ILs)
and erythropoietin (Epo)
