TISSUE HORMONES

1. TISSUE HORMONES OR PARA HORMONES M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.

2. PARA HORMONES • Tissue hormones • Local hormones • Act on the tissue on which they are produced • Short lived • Paracrine in nature • Eg: melatonin, renal hormones, eicosanoids and opiate peptides

3. Melatonin • Pineal gland or epiphysis hormone • Tiny conical or pine-like organ • On the dorsal side of brain in vertebrates lying deep in the groove b/n cerebellum and cerebral hemispheres • Clock work gland • Sphincter of thought – the mind’s valve • The seat of the rational soul • A neurological transducer : a system that converts nerve – type signal into an endocrine signal • Very well developed in children and shrinks after the 7th year and reduced to a little knot after puberty • Weighs less than a button

4. structure • Pineal secretes a hormone – melatonin • Melatonin inhibits the secretion of LH • Serotonin is the precursor under the influence of 2 enzymes • N-acetyl transferase (NAT) • Hydroxyindole-0-methyltransferase (HIOMT) • Pineal manufactures melatonin only in the night • It does not sit idle and converts Try into serotonin which accumulates and stored in inactive form until night • Neurotransmitters like NEP ↑ NAT & HIOMT • Exposure to light slows while exposure to darkness stimulates the production of melatonin • Pineal is under the control of sp.nerve cells found in hypothalamus called supra chiasmatic nuclei (SCN) • SCN turns melatonin production on & off in the pineal by directing the nightly increase in NAT

5. Functions • In humans, the glands rhythm may affect the sleep cycle • Melatonin makes people drowsy (sleeping aide) • Prevents cancer • Strengthens the immune system • This miracle hormone keeps a person using it away from growing old • Melatonin production ↓ age • Regulates menstrual cycle in females • Regulates sperm production in males

6. Renal Hormones • Kidney secrets 2 hormones • 1. Erythropoietin/Erythrocyte stimulating factor ESF • 2. Renin • ESF: secretion is stimulated by androgens and cobalt • Initially secreted as inactive protein called Renal Erythropoietin Factor (REF) • REF is like an enzyme converts plasma globulin into active erythropoietin • Glycoprotein – 8-12% hexose – 60000 • Lacks Met • Its activity is retarded by antibiotic actinomycin D and also by proteolytic enzymes • ESF stimulates Bone marrow ↑ no.of proerythroblasts ↑ reticulocytes (precursor of erythrocytes) • Stimulates the synthesis of a very large RNA ( 150S) by bone marrow cells

7. Renin • Catalyzes the synthesis of angiotensins • Angiotensins  vasoconstriction in kidneys  electrolyte & water retention in the body • This system  renin-angiotensin system • ↑ renal pressure , ↑ plasma Na+ , ↑ angiotensins  ↓ renin production

8. Eicosanoid hormones • Eicosanoids • FA derivatives • Involved in reproductive function • In the inflammation • In fever & pain • In the formation of blood clots • In the regulation of blood pressure • In gastric acid secretion

9. Eicosanoids • Derived from Arachidonic acid • Also called signal molecules • 3 types • 1.Prostaglandins • 2. Prostacyclins & thromboxanes • 3. Leucotrienes

10. Prostaglandins • Von Euler 1935 • Lipid soluble acidic substances • Semen is the richest source • Also found in Brain, spinal cord, thymus, lungs, pancreas, kidneys, menstrual fluid and placenta • Resembles prostanoic acid • Hydroxy derivatives of poly unsaturated FAs • Can be divided into 9 groups (A to I) • PGE  ether soluble , has a keto group at C9 • PGF  phosphate buffer soluble, a –OH group at C9

11. Prostaglandins • Half life 5 mins • Destroyed rapidly • High turn over rate • The most revolutionary therapeutic substances • Affects smooth muscles and bp • Often the activities of individual PGs oppose one another • Eg: PGE2 dialates blood vessels and bronchi • PGF2α constricts

12. Functions • Contraction and relaxation of the smooth muscles of the uterus especially at the time of ovulation • This may be due to chelation of Ca • 1ng/ml can cause contraction • Thus it resembles oxytocin • ↓ bp • ↓ lipolysis in AT ↓ conversion of ATP to cAMP • ↓ platelet aggregation • PGs have opposite effect on EP, NEP, glucagon, ACTH on the release of FAs from AT • Affects CVS (behaves both pressor and depressor agents) • Appear to control the secretion of gastric HCl • Have some beneficial effect in the control of the acid-induced gastric ulcers • Effect on reproductive system- male fertility • Low PGs in human semen is related to infertility • Also involved in inflammatory reaction & pain • anti-inflammatory drug such as aspirin , act by inhibitin the synthesis of PGs

13. Thromboxanes and prostacyclins • TXAs and PGIs are structurally related both arise from nascent PG • TXA2 was first isolated from platelets • PGI2 produced primarily in blood vessels • TXAs and PGIs displays a critical balance required for the normal functioning in the body • TXA2 is a highly effective vasoconstrictor and platelet aggregator • PGI2 is a potent vasodialator and inhibitor or platelet aggregation

14. Functions • PGIs inhibits platelet aggregation • PGIs relaxes coronary arteries • PGIs lowers BP • TXAs stimulates platelet aggregation • TXAs constricts coronary arteries • TXAs raises BP

15. Leukotrienes (LTs) • Precursor: Arachidonate • Enzyme : lipoxygenase • Cysteinyl-containing derivatives of arachidonic acid with a series of 3 conjugated double bonds • Eg: LTB4, LTC4, LTD4, LTE4 • Neutrophils make one class of LTs to alter mobility and act as chemotactic agents • Mast cells make another class ( formerly known as slow-reacting substances) which are responsible for bronchial constriction and other anaphylactic allergic reactions • Over production of LTs cause asthamatic attacks and also stimulates mucus secretion

16. Opiate peptides • 3 families • Enkephalins : consist of 5-7 amino acids • Derived from proenkephalin • Isolated from extracts of brain & pituitary and exhibit morphine like properties • Dynorphins: 10-17 AAs • Derived from prodynorphin • Endogenous compounds made in several locations • Major locations: brain, pituitary, adrenal medulla, and peptidergic neurons • Endorphins: 16-27 AAs • Proopiomelanocortin (POMC) • Isolated from extracts of brain, pituitary & exhibit morphine like properties

17. PHEROMONES • Social hormones • Smell signals • Species specific chemical substances • 1982 survey in USA on taste & smell • Strong link b/n sex and smell • Odour which are released from animals into the environment and evoke behavioural, developmental and reproductive responses • Karlson & Luscher

18. Pheromones • Pheromones work on the other members of the same species (hormones ?) • Pheromones are produced in glands and discharged externally to influence other members of the same species • Well known sex attractants

19. Structure • Chemically diverse group • AAs, Lipids, alcohols, org.acids • Female silk worm moth (Bombax mori) secretes a sex-attractant which attracts male moths • It is a long chain alcohol ( C16H30O) • With 2 double bonds C10 & C12

20. Structure • Insects also secrete alarm pheromones • Many of these are hydrocarbons, oxidized hydrocarbons, terpenoid in nature • Eg: Tridecane, Heptan-2-one, Citronellal, α-pinene

21. Types of pheromones • Based on their function, 2 types • 1. Releaser pheromones: stimulate specific patterns of behaviour • Powerful sex-attractants, mark-territories or trails • They initiate alarm reactions or bring about aggregation of individuals • 2. Primer pheromones: • They trigger physiological changes in endocrine activity esp related to sexual maturation, growth or metamorphosis

22. Examples • In the honey bee colony, the Queen bee secretes ‘Queen substance’ which inhibits the growth of ovaries in the worker bees. • The honey bee inject an alarm substance called 2- heptanone in the body of the victim it stings • Synthetically produced restenol can give the right fragnance to make love • Androstenone, a hormone found in perspiration from the armpit and genitals is found more in men than women • Couplins are estrogen dependent fatty acids found in vaginal secretions of some women • The testes form a steroid called priapol ( trivial name)

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