BIOCHEM-Molecular Endocrinology 1

 

SUBJECT: BIOCHEMISTRY

 

TOPIC: MOLECULAR ENDOCRINOLOGY 1

 

LECTURER: DRA. UY

 

DATE: JANUARY 2011

   

Hormone Receptors Biomedical Importance of Hormones 

Survival of multicellular organism



Intercellular communication (for survival)



Nervous system and endocrine system (as a whole)



They coordinate metabolism in the body



They are substances that carry information from sensor cells, which senses changes in the environment (electrolyte iimbalance, anoxia or hypoxia or low blood sugar level) to target cells, which respond to these changes o

Biochemical and physiological way of defining a hormone

Hormones Can be categorized by the site of synthesis: 1. Endocrine hormones – are synthesized by endocrine glands and transported by the blood to their target cells. - Production of hormone is faraway from the target 2. Paracrine hormones - are synthesized near their targets of action (ex. intestine) 3. Autocrine hormones – affect the cells that synthesize them

Hormones are present at very low concentrations in the ECF (compared to other proteins in ECF) *they have to be low since hormones causes significant changes when not controlled or plenty; in signalling pathway, one hormone can amplify millions and millions of response



Hormones





High degree of discrimination is provided by cellassociated recognition molecules -> RECEPTORS *receptor – protein; recogniton molecule



Hormones initiate their biologic effects by binding to the receptors



A target cell is defined by its ability to the selectively bind a given hormone to its cognate receptors

*Hormone receptors are selective and specific. Each of the cells will have its own receptors or binding sites of hormones. Low amount of hormone in the ECF will bind right away to the receptor and initiate the biologic effect. There is an amplification of signals in the binding of hormone and receptor. Classification of hormones by mechanism of action 1. Hormones that bind to intracellular receptors 

Androgens



Cacitriol (1,25(OH)2-D3)



Estrogens



Glucocorticoids



Mineralocorticoids

Hormones are also categorized by Chemical Structure:



Progestins

1. Proteins or peptides – ex: insulin, glucagon; synthesized as larger precursors that undergo processing and secretion.



Retinoic Acid



Thyroid Hormones (T3 and T4)

2. Amino Acid derivatives – cathecolamines and thyroid hormones

*PETCAT – Progesterone, Estrogen, Testosterone, Cortisol, Aldosterol, Thyroid Hormones (mnemonic)

Ex: Triiodothyronine, T3, T4, Epinephrine, Norepinephrine, Levothyroxine, Thyroxine

2. Hormones that bind to cell surface receptors

*tyrosine – very important amino acids

A.

The second messenger is cAMP 

a2 -adrenergic catecholamines



B – Adrenergic catecholamines

3. Fatty acid derivatives – eicosanoids (ex.prostaglandins)



Adrenocorticotropic hormone (ACTH)



Antidiuretic Hormne (ADH)

4. Cholesterol derivatives – steroids



Calcitonin

5. Gases – nitric oxide (not a hormone in the strict sense of the word but it can act on target cells)



Chorionic gonadotropin, Human (hCG)



Corticotropin-releasing Hormone



FSH



Glucagon

*TSH is not a thyroid hormone but a pituitary hormone!

*In the endothelial Nitric oxide synthase (ENOS)

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Page 1



Lipotropin (LPH)



LH



Melanocyte-stimulating hormone (MSH)



Parathyroid Hormone (PTH)



Somatostatin



Thyroid-stimulating hormone (TSH)

Hormone Complex

B. The second messenger is cGMP 

Atrial Natriuretic Factor



Nitric Oxide

C. The second messenger is calcium or phosphatidylinositol (or both) 

Acetylcholine (muscarinic)



a1 – Adrenergic catecholamines



Angiotensin II



Antidiuretic Hormone (vasopressin)



Cholecystokinin



Gastrin



Gonadotropin Releasing Hormone



Oxytocin



Platelet-derived growth factor (PDGF)



Substance P



Thyrotropin-releasing hormone (TRH)

Diversity of Endocrine System 

Hormones are synthesized in a variety of cellular arrangements



Discrete Organs – Thyroid, Pituitary and Adrenals

*what they are is what they secrete Organs perform 2 distinct but closely related funtions: 

Ovaries – mature oocytes and estradiol and progesterone



Testes – mature spermatozoa and testosterone

*this testosterone is weak compared to DHT (dihydrotestosterone Specialicez cell within other organs: 

Small intestine – glucagon like peptide (targets for new medication in diabetes)



Thyroid – calcitonin (action is in bones and parathyroid)



Kidney – Angiotensin II (control of blood pressure; target for all Angiotensin II blockers) *kidneys also produces eryhtopoietin

D. The second messenger is a kinase or phosphatase cascade

Parenchymal Cells of more than one organ:



Adiponectin



Chrionic somatomammotropin



Epidermal growth factor



Erythropoietin



Fibroblast growth factor (FGF)



Growth Hormone (GH)



Insulin



Insulin-like growth factors I and II

 17B – estradiol



Leptin

 Testosterone



Nerve growth factor (NGF)

 Cortisol



Platelet-derived growth factor

 Progesterone



Prolactin

 1,25 (OH)2 – D3



Skin, liver, kidney – calcitriol (vitamin B3)

Hormones are chemically diverse 

They are synthesizied from a wide variety of chemical building blocks: o

Cholesterol Derivatives (all ssteroid hormones came here)

*common to them is the cyclopentanoperhydropenantrene ring

General Feature of Hormone Classes GROUP 1

GROUP 2

Steroid, iodothyronines, calcitriol, retinoids

Polypeptides, proteins, glycoproteins, catecholamines

Solubility

Lipophilic/ Hydrophobic

Hydrophilic/ Liphophobic

Transport Proteins

Yes

No

Plasma Half-Life

Long (hrs- days)

Short (min.)

Receptor

Intracellular

Plasma Membrane

Mediator

Receptor-

cAMP,cGMP,

Types

Ca2+, metabolites of complex phosphoinositols, kinase cascades

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

o

Tyrosine 

T3 and T4



Norepinephrine



Epinephrine

o

Iodine – very important building bloackof Thyroxine or the thyroid hormone

o

Polypeptides

o



TRH



ACTH

Glycoproteins (TSH, FSH, LH) 

Common a subunits



Unique b subunits Page 2

*all of glycoproteins have a common a subunits but differ in be subunites *very low cholesterol can lead to brain tumors Hormones are synthesized and modified for full activity in variety of ways: 

Hormones synthesized in final form and secreted immediately: those derived from cholesterol; ACTH



Hormones synthesized in final form and stored: catecholamines; fight and flight response



Those synthesized from precursor molecules, then processed and secreted upon cue: insulin (cue for insulin is hyperglycemia or high blood glucose) *blood sugar level is important in release of pancreatic hormones



Those converted to active forms from precursor molecules in the periphery: thyroid hormones and DHT *thyroid hormones is more secreted as T4 and peripherally converted to T3 which is more active of the two.

Adrenal Steroid Hormones 

Adrenal steroid hormones are synthesized

from cholesterol. An ACTH – dependent 

steroidogenic acute regulatory (STaR) protein is essential for the transport of cholesterol to p450 scc (side chain cleavage) in the inner mitochondrial membrane.

*cholesterol in P450 scc will be cleaved to produce pregnenolone and isocaproaldehyde 

All mammalian steroid hormones are formed from cholesterol via pregnenolone through series of reactions (shuttling) occurring either in the mitochondria or ER of the adrenal cell.

*adrenecorticotrophin and ACTH is the same

*this image is very important! *17  - Hydroxylase – if this enzyme act first (along with 17,20 lyase), you will produce dehydroepiandosterone (for masculinity) *3B – hydroxysteroid dehydrogenase isomerase – regulator and should act first than 17a- hydroxylase so that hormones can be regulated; progesterone will be produced from pregnenolone *There is cellular specificity in adrenal steroidogenesis* *there are three zones in the adrenal cortex: zona glomerulosa, zona fasciculate and zona reticularis *Aldosterone synthesis will occur only in the zona glomerulosa cells because the enzymes 18 – hydroxylase (aldosterone synthase) & 18 – hydroxysteroid dehydrogenase are found only in that region. *aldosterone acts on the renin-angiotensin-aldosteronesystem for blood pressure *most common problem of mutation or deficiency in the adrenal gland is the 21 hydroxylase enzyme (deficiency is also called the masculinization syndrome since deficiency in this enzyme, you will have abundant masculine hormones since the formation of aldosterone and cortisol is blocked) *17  - Hydroxylase and 21- hydroxylase are smooth ER enzymes while 11  - hydroxylase is a mitochondrial enzyme. *Steroidogenesis - involves the repeated shuttling of substrates into and out of the mitochondria. (along the way they will be caught by other proteins during shuttling problem) *adrenal medulla produces cathecolamines

*basic steroid hormones – differ only in attachment

adrenal cortex produces the thyroid hormones Testicular Steroidogenesis 

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Immediate precursor is cholesterol

Page 3





Rate limiting step: delivery of cholesterol into the inner membrane of the mitochondria by the STaR protein The conversion of cholesterol to pregnenolone in the ovary & testes is promoted by LH rather than ACTH.

*ACTH is responsible for children, but as you grow up it is the LH

Ovarian Steroidogenesis Estrogen are of 3 types:   

17  - Estradiol is the primary estrogen of ovarian origin; most potent of the three; responsible for femininity; Estriol is abundant estrogen during pregnancy; this comes from the placenta; Estrone – abundant when post-menopausal since there are no more production of 17B-estradiol;

*female cannot live without men since you cannot have estradiol comes from testosterone. *Aromatase – very important enzyme; responsible for female odor (in dogs: pheromones); Aromatase is responsible for synthesizing estradiol from testosterone and also converts androstenodione to estrone. *16a-hydroxylase- converts estrone to estriol; abundant in placenta during preganancy *progesterone also comes from pregnenolone; Progesterone is also more fluid-retaining than other estradiol thus when at the end of the term there is edema formation because of increase in progesterone Biosynthesis of Estrogen

*At the adrenals, the final form is the androstenedione and dehydroepiandrosterone, but in the testicular level meaning males, they will be converted to Testosterone through the enzyme 17B-hydroxysteroid dehydrogenase (in Dehydroepiandrosterone, it first become androstenodione before testosterone.) *This happens when the child is in puberty (testicular steroidogenesis). Adrenal steroidogenesis happens even before puberty. *Dihydrotestosterone is formed from Testosterone in Peripheral Tissues (prostate and testis). DHT is most potent even than testosterone. DHT is the cause of the benign prostatic hypertrophy too much production of DHT) *The most significant Metabolic product of testosterone is DHT, the active form of this hormone. DHT is an active metabolite since it got another H+. * 5a-reductase +NADPH – another important enzyme and another important cofactor; for reduction process from Testosterone to DHT. *5a-reductase inhibitor is used for treating benign prostatic hypertrophy. Ex: Xatral, Finasteral, Dutasteride

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Page 4

*1, 25 (OH)2 – D3 (Calcitriol) is synthesized from a Cholesterol Derivative; needs 3 organs to be formed; *7-Dehydrocholesterol comes from the adrenal. With the action of the sunlight on the skin, you will form previtamin D3 and then the liver you have 3 different enzymes:   

25 Hydroxylase – Forms 25Hydroxycholecalciferol (25[OH]-D3) and activated by the following 2 hydroxylases 24-hydroxylase – forms 24,25 (OH)2-D3 1a- hydroxylase – forms 1,25 (OH)2-D3 (calcitriol)

*Both 24-hydroxylase and 1a-hydroxylase are needed for the formation of the 1,24,25 (OH)3-D3

Catecholamines & Thyroid Hormones - made from Tyrosine  

Catecholamines are synthesized in final form and stored in secretion granules. Epinephrine – major product of adrenal medulla (80%) - not made in extramedullary tissue

*Tyrosine is the immediate precursor of catecholamines. *Tyrosine hydroxylase is the rate-limiting enzyme in the catecholamine synthesis that forms Dopa from Tyrosine *Dopa carboxylase – forms dopamine from Dopa *Dopamine b-hydroxylase – forms Norepinephrine from dopamine. *PNMT (phenylethanolamine-N-methytransferase – forms epinephrine from norepinephrine. *Catecholamines cannot cross the blood, brain barrier; hence in the brain they must be synthesized locally. *Parkinson’s disease - a CNS disorder where there is local deficiency of dopamine synthesis; symptom: shuffling gait * L- Dopa (levodopa or sinemet) - important agent in treatment of Parkinson’s disease since it readily crosses the BBB (blood brain barrier; you will produce Dopamine *aromatase – responsible in patient with cirrhosis or hepatic enceopathy in which they have a problem where the androstenedione will be converted to estrediol so you will have estrogenezation of the males. Males with this wil have big breasts and some are even milking. Aromatase are abundant in liver and in adipose tissues (thus fat = boobs) Thyroid Hormone Synthesis: 1. These hormones require Iodine, a rare element, for bioactivity 2. They are synthesized as part of a very large precursor molecule (thyroglobulin) 3. They are stored in an intracellular reservoir (colloid). 4. There is peripheral conversion of T4 to T3

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Page 5

*if all T4 are converted to T3 immediately, you wll have hyperthyroidism or very fast metabolism *NADPH, oxygen, tyrosine and iodine is needed in this processes *Thyroglobulic iodination – iodination of thyroglubulin after Iodine was oxidized by peroxidase coming from the capturing of NADPH of oxygen and H+

*to test for the diabetes, you need to test for C peptide (connecting) since they will be cleaved in the liver and are the active ones. This mean it will not be destroyed since it will not be stored for so long and recycled. Parathyroid Hormone (PTH) • Secreted as 84 – amino acid peptide

*Coupling of the MIT and DIT will result to T3. Coupling of the DIT with DT results to T4. This stored intracellularly as a colloid that is part of large precursor molecule called the thyroglobulin. As the demand increases for T3 and T4, the more T3 and T4 is released extracellularly.

• a decrease in Ca+  marked increase in PTH synthesis & secretion

*Na+-K+ ATPase trasporter is also needed in this pathway.

• Also has a C-fragment sequence

• its biosynthesis & secretion are regulated by the plasma ionized Ca+ concentratio

*All are from the anterior pituitary except PTH.

Insulin:  

synthesized as a prohormone & modified within the  - cell. one of the hormones made from larger peptide precursors made up of: o Connecting peptide – produced from liver; connects a-chains and B-chains o a-chains – has a intra-sulfide bond (Cys11 – Cys6) o B-chains –

*a-chains & B-chains - has 2 separate inter-sulfide bonds (bet. Cys20 of alpha and Cys19 of Beta and bet. 2 Cys7) *insulin in the market is modified in the B-chains.

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

*Angiotensin II is also synthesized from a large precursor; is also involved in aldosterione regulation *The RAS is involved in the regulation, of BP and electrolyte metabolism (thru aldosterone production) *In the diagram below, Angiotensinogen is converted by Renin to Angiotensin I. Angiotensin - converting Enzyme converts Angiotensin I to II which is acted upon by Aminopeptidase to for Angiotensin III. Degradation products are formed by angiontensinases from angiotensin III. The active form is the angiotensin II.

Page 6

Binding Specificity

Very High

Low

Saturability

Yes

No

Reversibility

Yes

Yes

Signal Transduction

Yes

No

Actions of Specific Hormones HYPOTHALAMIC HORMONES •VASOPRESSIN and OXYTOCIN •OTHER HORMONES that regulate the synthesis and release of hormones from the anterior pituitary HORMONES OF THE ANTERIOR PITUITARY •PROLACTINOMA - the most common tumor of the pituitary - double vision, amenorrhea, and galactorrhea •Hyperprolactinona Pro-opiomelanocortin (POMC) Peptide Family  

consists of peptides that act as hormones (ACTH, LPH, MSH) & others that may serve as neurotransmitters or neuromodulators (endorphins) Products of POMC cleavage: o ACTH  a-MSH  CLIP (corticotropin-like intermediate lobe peptide) o B-LPH (lipotropin)  y-LPH  B-endorphin  B-MSH  y-Endorphin  a-Endorphin

- can result from drugs that inhibit dopamine action: antipsychotic drugs (Thorazine) *Galactorrhea – letting down of milk; spontaneous flow of mlik •GROWTH HORMONE (GH): - Stimulates release of insulin-like growth factors (somatomedin) - Antagonizes the effects of insulin on carbohydrates and fat metabolism - its release is inhibited by somatostatin •THYROID - STIMULATING HORMONE - Stimulates the release of T3 and T4 from the thyroid gland.

Diversity in the Storage of Hormones Hormone

Supply Store Cell

Steroid and 1,25 (OH)2-D3

None

Catecholamines and PTH

Hours

Insulin

Days

T3 and T4

Weeks

- released from anterior pituitary through the signal of the TSHRH from hypothalamus - used to screen patients for thyroid disease. - elevated levels suggest hypothyroidism (negative feedback) - low levels suggest hyperthyroidism (negative feedback)

*no patient will suffer from hypo or hyperthyroidism immediately. Hyperthyroidism is a suttle disease. It can occur years after you have thyroidectomy.

*If patient has hyperthyroidism, the feedback mechanism signals the anterior pituitary to decrease the release TSH. The same can be said to those hypothyroidism.

*Type I diabetic patients can survive without insulin for 4-5 days and until day become coma.

•LH and FSH:

*Catecholamines and PTH stores for hours that’s why you can have an adrenaline rush for hours and feel week after.

- stimulates the GONADS to release hormones that are involved in reproduction

Comparison of Receptors with Transport Proteins Feature

Receptors

Transport Protein

- their release is stimulated by GnRH and inhibited by GnIH from the hypothalamus

Concentration

Very Low (thousands/cell)

Very High (billions/uL)

•Protein product of the PRO-OPIOMELANOCORTIN gene

Binding affinity

High (pmol – nmol/L range)

Low (umol/L range)

- produced in response to CRH from the hypothalamus

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Page 7

- cleaved to generate a number of peptides: 1. ACTH – cortisol ; has permissive effect on production of aldosterone 2. Lipotropin (LPH)- cleaved to form MSH and endorphins *If you have a pituitary problem that involves this, there will be a darkening of the skin. THYROID HORMONE •T3 is more active than T4

- Cortisol and Epinephrine act in concert to supply fuels to the blood so that energy can be produced to combat stressful situations - Anti-inflammatory effects: induce synthesis of lipocortin which inhibits phospholipase A2, rate limiting enzyme of protaglandin synthesis . - Suppress the immuned response by causing lysis of lymphocytes

•Most T3 is produced by deiodination of T4

- Influence metabolism by causing movement of fuels from peripheral tissues to the liver

•During starvation,T4 is converted to reversed T3 (RT3), which is not active

- Promotes gluconeogenesis by inducing synthesis of PEPCK

•Binds to nuclear receptors and regulates the expression of many genes.

HYPERCORTISOLEMIA

•Needed for growth, development, and maintenance of almost all tissues

•likelihood of infection

•Stimulates oxidative metabolism and causes basal metabolic rate to increase

•BONES : osteoporosis

•Glucose CNS effects: hyperirritability or depression •Muscle : loss of protein leading to weakness

•HYPOTHYROIDISM

•Thinning of dermal and epidermal structures: striae

- Generation of ATP id reduced, causing a sense of weakness, fatigue, and hypokinesis

•Increased vascular fragility : easy bruising •Increased intolerance or overt diabetes

-the reduced BMR is assoc with decreased heat production, causing cold intolerance and decreased sweating.

•Central obesity: buffalo hump and moon facies

- Less demand for delivery of fuels and oxygen to peripheral tissues hence circulation is slowed, decreased heart rate and BP

•CUSHING SYNDROME - If caused by excessive production of cortisol by an adrenal tumor or by intake of exogenous glucocorticoids

•HYPERTHYROIDISM

•CUSHING DISEASE

-BMR is increased because the rate of oxidation of fuels by muscles and other tissues is increased.

- hypercortisolemia caused by excessive secretion of ACTH by a pituitary tumor

- increased heat production: heat intolerance and increased sweating

•EPINEPHRINE

-elevated tone of sympathetics: inc HR and BP - Weight loss is severe because of excessive rate of fuel oxidation HORMONES that STIMULATE GROWTH

- Increases blood glucose by stimulating liver glycogenolysis - Stimulates lipolysis in adipose tissue and glycogen degredation in muscle - Makes fuels available for “fight or flight”

•INSULIN and GH •GH antagonizes many of the metabolic actions of INSULIN, stimulating gluconeogenesis and promoting lipolysis.

HORMONES that REGULATE SALT and WATER BALANCE

•Alternative fuels are therefore made available so that muscle protein can be preserved

-causes the production of proteins in cells of the distal tubule and the collecting ducts of the kidney:

•GIGANTISM

1. Permease is produced that allows sodium to enter cells from the lumen

- Caused by excessive secretion of GH as a result of a benign tumor of the ant pituitary gland and the hypersecretion begins before closures of the growth centers in the long bones •ACROMEGALY - if hypersecretion begins after the growth centers have closed HORMONES THAT MEDIATE THE RESPONSE TO STRESS •GLUCOCORTICOIDS

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

•ALDOSTERONE

2. Citrate synthase is induced ( inc TCA hence ATP production) 3. Na-K ATPase pump is induced - K and H ions are lost; Na is retained; water is resorbed; blood volume and pressure are increased •PRIMARY HYPERALDOSTERONISM - Conn Syndrome - aldosterone-secreting tumor of adrenal gland - sodium retention and potassium secretion with resultant hypertension and hypokalemia Page 8

•ADDISON DISEASE - loss of adrenocortical steroids - the mineralocorticoid deficiency leads to: loss of sodium ions and water in the urine and reciprocal potassium retention (hyperkalemia), and hydrogen ions (mild met.acidosis) - reduction in BP HORMONES THAT CONTROL PRODUCTION

•LH stimulates Leydig cells to produce and secrete testosterone. •FSH acts on Sertoli cells to promote the synthesis of androgen-binding protein (ABP). •ABP binds testosterone and transports it to site of spermatogenesis, where testosterone is converted to DHT by 5-α-reductase. •Testosterone is responsible for masculinization during early devpt, and at puberty,sexual maturation of the male. •5-α-reductase: - required for normal male development.

The Action of FSH and LH on the OVARY •The Menstrual Cycle 1.FSH acts on the follicles to promote maturation of ovum and to stimulate estradiol production and secretion.

- genetic deficiency results in a phenotype similar to androgen insensitivity syndrome. - drugs that inhibit this enzyme (ex: finasteride) are used to inhibit the effects of DHT in males,like male pattern baldness and BPH.

2. Estradiol causes thickening and vascularization of uterine endometrium. 3. LH surge at midcycle stimulates ovulation, formation of corpus luteum and secretion of progesterone and estradiol. 4.Progesterone causes the endometrium to continue to thicken and increase its secretory capacity. •Events in the Absence of Fertilization 1. Corpus luteum regresses due to declining LH levels. Progesterone and estradiol levels decrease. 2. Low steroid hormone levels cause the cells to die and the endometrium is sloughed off (menstruation). •Oral contraceptive pills – have low levels of estrogen and progestin derivatives. - reduce both LH and FSH levels. - destroy the normal cyclicity of hormones and result in a failure to ovulate prevent conception. •Events following Fertilization 1. Corpus luteum is maintained initially by hCG. 2.Subsequently, the placenta produces hCG and progesterone. 3.After the corpus luteum dies,placenta continues to produce large amts.of progesterone.

HORMONES THAT PROMOTE LACTATION PREPARATION OF THE MAMMARY GLAND FOR LACTATION •Prolactin, glucocorticoids, and insulin are the major hormones responsible for the differentiation of mammary alveolar cells into secretory cells. •Prolactin stimulates the synthesis of milk proteins, casein and α-lactalbumin. •Progesterone inhibits milk protein production and secretion during pregnancy. •At term,when proesterone levels fall, the inhibition of milk protein synthesis is relieved. *Dopamine – inhibit release of prolactin REGULATION OF MILK SECRETION DURING LACTATION •Prolactin causes milk proteins to be produced and secreted into the alveolar lumen. •Oxytocin causes contraction of the myoepithelial cells surrounding the alveolar cells and the lumen, and milk is ejected through the nipple. •The secretion of both PRL and OT by the pituitary is stimulated by the suckling of the infant and by other factors. HORMONES INVOLVED IN GROWTH AND DIFFERENTIATION

4. Near term, progesterone levels fall.

•Retinoids are produced in the body from dietary Vit. A.The major source,β-carotene, is cleaved into 2 molecules of retinal.

5. PGF2α and oxytocin stimulate uterine contractions, and the infant is delivered.

•Retinal (an aldehyde) and retinol (an alcohol) are interconverted by oxidation and reduction reactions.

•Pregnancy Tests

•Retinoic acid is produced by oxidation of retinal and cannot be reduced.

- detect the presence of hCG in the urine.

•Retinol,the transport form,is stored as retinyl esters.

- serum quantitation of hCG levels can be used to differentiate a normal intrauterine pregnancy from an ectopic pregnancy.

•Retinal is a funtional component of the visual cycle reactions.

•Pitocin – synthetic form of OT that can be administered during labor to initiate or augment labor.

•Retinoic acid is involved in growth and also in differentiation and maintenance of epithelial tissue HORMONES THAT REGULATE CALCIUM METABOLISM

The Action of FSH and LH on the Testis BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

•Parathyroid hormone (PTH), 1,25-DHC,and Calcitonin are the major regulators of Ca metab. Page 9

•PTH, produced in response to low Ca levels,acts to increase Ca levels in the ECF. •1,25-DHC stimulates the synthesis of a protein involved in Ca absorption by intestinal epithelial cells. Calcitonin lowers Ca levels by inhibiting its release from bone and stimulating its excretion •HYPERPARATHYROIDISM- patients can present with fractures of long bones,renal stones, GI disturbance,lethargy and weakness. 1. Primary – the result of tumor of the parathyroid gland. 2. Secondary – as a result of renal failure. •HYPOPARATHYROIDISM –most often due to trauma to the parathyroids during surgery of the thyroids HORMONES THAT REGULATE UTILIZATION OF NUTRIENTS

•GASTRINOMAS - gastrin-secreting endocrine tumors associated with Zollinger-Ellison syndrome. - increased hydrochloric acid production with resultant recurrent peptic ulcers. •VIPomas - rare tumors that secrete VIP - watery diarrhea, hypokalemia, and achlorhydria INSULIN AND GLUCAGON •INSULIN - elevated in the fed state - promotes storage of fuels: glycogen and triacylglycerol. - stimulates glucose transport into muscle and adipose cells. - stimulates protein synthesis and growth

GUT HORMONES •Gastrin from gastric antrum and the duodenum stimulates gastric acid and pepsin secretion.

•GLUCAGON

•Cholecystokinin (CCK) from the duodenum and jejunum stimulates contraction of the GB and secretion of pancreatic enzymes.

- increases the availability of fuels and fatty acids) in the blood.

(glucose

- stimulates glycogen degradation in the NOT in muscle.

liver but

•Secretin from duodenum and jejunum stimulates the secretion of bicarbonate by the pancreas. •Gastric inhibitory polypeptide (GIP) from the small bowel enhances insulin release and inhibit gastric acid secretion Vasoactive intestinal polypeptide (VIP) from the pancreas relaxes smooth muscles and stimulates bicarbonate secretion by the pancreas

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

- elevated during fasting

- stimulates gluconeogenesis and lipolysis in adipose tissue.

Page 10

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Page 11

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Page 12

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Page 13

BIOCHEMISTRY – MOLECULAR ENDOCRINOLOGY 1

Page 14