Endocrinology, lecture on Prolactin
USD Department of Biology
Endocrinology
Summers
Hormones
Endocrine Glands
Receptors
Homeostasis
2nd Messengers
Nuclear Receptors
Genetic Regulation
Hormone Synthesis
Receptor Regulation
Hypothalamo-Hypophysial Communication
Tropic Hormones
Neurohypophysial Nonapeptides
Thyroid Axis
Steroids
Adrenal Axis
Adrenal Medulla
Osmotic-Pressure Balance
Reproductive Endocrinology
Prolactin
Somatic Axis
Growth Factors
Immune Factors
Ca++, PO4 Homeostasis
Pancreatic Hormones
GI Hormones
Guts 'n Brains
Brain Hormones
Neurosteroids
Neuropeptides
Endocrine Evolution
Figures for Endocrionology
text:Vertebrate Endocrinology5th Edition - David O. Norris:
Read pages 112-115, 129-131, 175-176, 355-356 for this lecture
acronyms    end
XX.  Prolactin and Growth Hormone 		video

	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. IGF1 stimulates PrL release

				i. GH ®+ IGF1

			c. 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]: 
			 PrL ®  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

					1) 	PrL ® PRL-R ® ERK				

					2) PrL ® PRL-R ® Tyr PK CSK (immune)

	D. PrL 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.  milk protein gene transcription & mRNA stability


			c. synergistically with E,  insulin, T3, B/F and IGF1

				i. 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)

XXII. Somatic Growth Axis