3.3 Prolactin and other tropic hormones Flashcards
Prolactin:
1. what type of hormone?
2. similar structure to which hormone? conserved what?
3. how many aa?
4. concentration high?
5. prolactin locus has how many genes?
- peptide hormone
- GH! conserved helix bundle protein
- 198 aa (vs 191 in GH)
- 0.1 mg/pituitary –> small compared to GH
- prolactin locus has 1 gene –> PRL
PROLACTIN:
1. circulates in which form? what is the most bioactive?
2. half life?
3. released in what fashion? + describe
4. sexual dimorphism
5. which type of cell in pituitary produces PRL?
- monomeric, dimeric or polymeric –> monomeric is the most bioactive
- 25-45 minutes –> fairly short
- episodic release: 4 to 14 pulses per day –> highest at 3-5am. lowest at 10pm-12am (?)
- females have more prolactin than males (levels reduce with age)
- lactotrophs
explain the primary regulation of prolactin
- what type?
- what proves it?
- explain functioning
- primary regulation by inhibition!
- destruction of median eminence increase PRL secretion, while decreasing pituitary hormones!
- dopamine neurons from arcuate nucleus produce dopamine = acts as main inhibitor via dopamine D2 receptors on lactotrophs
does PRL have positive or negative effect on dopamine neurons? to complete feedback loop
- dopamine neurons express what receptor?
positive!
- dopamine inhibits PRL
- so to complete feedback loop, PRL will positively activate dopamine neurons through the prolactin receptor on dopamine neurons so that PRL synthesis/release is even more inhibited
- what positively regulates prolactin production?
- what role does estrogen have in prolactin regulation
- does oxytocin inhibit or promote PRL? how? what stimulus?
- Putative PRL-releasing factors –> PRF neurons have been identified in various parts of brain –> TRH, VIP and oxytocin –> positively regulate PRL
- estrogen inhibits dopamine neurons and activates lactotrophs = promotes PRL
- suckling stimulus activates oxytocin neurons –> inhibits dopamine neurons = promote PRL
prolactin signals through which pathway?
- 2 types of dimerization
- through RTK with recruited kinase activity –> JAK2 pathway –> stat OR ERK OR PI3K pathways
- ligand dependant dimerization (PRL binds to 1 part, then recruits 2nd half for dimerization) OR ligand-independent dimerization (already dimerized, then PRL binds to receptor)
where are prolactin receptors expressed?
- in breast tissue!
- but also in many other tissues like pituitary, liver, adrenal cortex, kidneys, prostate, ovary, testes, intestine, epidermis, pancreatic islets, lung, myocardium, brain and lymphocytes
what is prolactin’s main function?
- distinct from which other function?
- PRL is essential for initiation and maintenance of milk production (hypophysectomy/ removal of pituitary gland) leads to immediate cessation of milk synthesis)
- prolactin stimulates milk synthesis in alveolar epithelial cells –> DISTINCT from neural regulation of milk ejection (which is enabled by instantaneous release of oxytocin in response to suckling –> oxytocin stimulates alveolar smooth muscles that surround each individual alveoli)
regulation of mammary gland development: WHICH HORMONES FOR:
- alveolar growth (4)
- duct system development (3)
ALVEOLAR GROWTH (epithelial cells and smooth muscles):
- PRL
- estrogen
- progesterone
- adrenal steroids
DUCT SYSTEM DEVELOPMENT (exocrine gland portion):
- GH
- estrogen
- adrenal steroids
PRL levels rise within ___-____ minutes of _________ and remain elevated for ___-____ minutes
- 1-3 minutes of suckling and remain elevated for 10-20 minutes (beyond the suckling)
describe coordinated effect of oxytocin and prolactin on milk production (gros schéma)
suckling –> positive effect on mechanoreceptors in nipple –> positive effect on hypothalamus:
1. nervous pathway to posterior pituitary –> increase oxytocin –> contraction of myoepithelial cells surrounding alveoli –> milk ejection
2. hypothalamus –> decrease prolactin inhibiting hormone (dopamine neurones) + increase prolactin-releasing hormone (TRH, VIP, oxytocin) –> positive effect on anterior pituitary which produces prolactin –> milk synthesis
normally PRL activates/inhibits dopamine neurons, but not during __________
- explain
- activates dopamine neurons to inhibit its own secretion
- negative regulation is slightly lowered –> sensitivity of PRLr on dopamine neurons is lower –> for continued milk availability (which explains why PRL levels remain elevated even after suckling cessation)
how does prolactin regulate reproductive system? explain
- involved in (negative) regulation of reproductive system
(hyperprolactinemic conditions associated with hypogonadism in males and females) - PRL = inhibition of ovarian cycle during pregnancy/lactation (especially in pigs! –> don’t resume estrus cycle until weaning (separation of young one from mother))
what are other functions of prolactin (apart from milk synthesis)? (4)
- regulation of reproductive system (inhibit ovarian cycle)
- immunomodulation: PRLr on B and T lymphocytes and macrophages
- PRL acts as a mitogen and promotes survival + promote proliferation and differentiation
- acts synergistically with many other hormones
what is ACTH and how is it synthesized?
adrenocorticotropin = ACTH
- derived by proteolytic cleavage of large precursor molecule pro-opiomelanocortin (POMC)
- POMC is a neurotransmitter –> cleaved to smaller peptides that become hormones –> ACTH is one of them –> all the smaller peptides/hormones are called POMC derived peptides OR ACTH related peptides