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28 Cards in this Set

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Male development


+SRY gene

+SRY gene in males causes differentiation of Sertoli and Leydig cells


-Sertoli cells produce AMH


-Ledig cells produce Testosterone


In absence of SRY


-Female phenotype differentiates

Masculinization

Testosterone (or Estrogen metabolites)


SDN-POA


SNB


Song nuclei

CAIS

Complete androgen insufficiency syndrome

Non-functional androgen receptor


Gonadol sex XY


Internal male XY


Individual IDs as female- has to have T, feel no ambiguity



Aromatase deficiency

Normal male phenotype


Yet in order to express normal male behavior, have to have androgen receptor

Tfm- x-linked AR gene mutation

Testicular feminization mutation


-Tfm males- feminine


-Tfm females


Mouse model


-Carriers of mutation

Gender ambiguity

Timing of hormone influence


Disorders of androgen synthesis and/or action affect embryonic development at 8 wk


Virulization of females with 21-hydroxylase deficiency does not commence until later in gestation


Adult males w/ 17(beta)HSD or 5(alpha) reductase deficiency may have androgen levels near normal as an adult despite profound defects in androgen action during embryogenesis

Gender identity


Gender ambiguity

21-hydroxylase- can't produce cortisol


17(beta)HSD - can't produce testosterone or DHT


5(alpha) reductase - born female - puberty will grow more penis than at birth, still considered female


-ID as male when only 5(alpha) reductase deficiency

Gender identity

Women lacking proper gonad function (no Estradiol) have female gender role/behavior (E2 minor role in female gender identity)


Men w/ Klinefelter syndrome form sufficient androgen during embryogenesis and induce male phenotype (Diminished androgen production after puberty - most have male gender role behavior)


46XY-Androgen resistance (Complete or partial)


-Female phenotype and behavior

Calcium regulation

Parathyroid hormone (PTH)


-Synthesized in the parathyroid gland


Calcitonin


-Synthesized in the C cells of the thyroid


Vitamin D


-Obtained in the diet or synthesized in the skin by UV radiation

Target tissue for PTH

Intestine


Bone


Kidney


Skin


Mammary gland

Calcium and Phosphorus

Required for normal growth and function


Plasma concentrations are regulated within a very narrow range (9.0-10.2 mg/dL Ca+)

Ca+, P homeostasis

Intestine


-Vitamin D increases intestinal absorption of Ca+ and P


--RDA for Ca+ = 800mg/d; Intestinal secretion adds 600mg/d; 900mg is absorbed from intestinal lumen (remainder is excreted in feces)


Bone (reservoir for Ca+ and P)


-Bone accretion and mobilization


-Normally 300mg of Ca+ is absorbed and replaced each day


Kidney


-Urinary excretion and reabsorption


Glomerulus filters 10,000Ca/d (100-300mg is excreted in urine)

Parathyroid hormone


(Protein hormone)

84aa


Synthesized as a larger hormone (post translational processing)


PTH is stored in secretory granules


-Released in response to decreased blood concentrations of Ca+


-Parathyroid gland recognition (receptor) sites for Ca+ (7 TM G-ptn coupled receptor)


Extra cellular domain has acidic sites-Ca+ binding domains (Ca+ bound to the Rt -- decrease cAMP)


Receptor is in places like the kidney, bone

Calcitonin (CT)

Protection against elevated Ca+ (hypercalcemia) (after a meal)


Promote bone mineralization


Protection against bone demineralization during Ca+ stress


-Pregnancy, lactation, Ca+ deprivation


--High levels observed during gestation and lactation; Inhibits osteoclast activity


Calcitonin levels are very low when blood concentrations of Ca+ are normal


-Stimulation of secretion in response to high Ca+


Secreted by thyroid gland (C cells or parafollicular cells)


Renal cortex


-Renal tubules have receptors for calcitonin


-Effect is small in humans (not important for the regulation of Ca+)

Vitamin D

Insufficiency linked to: Bone anomalies, cancers, diabetes, depression, MS, autoimmunity, cardiovascular disorders and other chronic diseases


Primary source-conversion of UVB rays to Vit D


-Many people do not get enough sun exposure


--High winter latitude, dark pigmentation, sunscreen use, cultural mores to cover the skin, lifestyles that limit outside time


Organic constituent necessary for life and development


Originally applied to cholecalciferol and ergocalciferol


-Ability to prevent/cure rickets (failure of the bone to ossify properly)

Vitamin D cont

Skin-liver-kidney production pathway


-Cholecalciferol produced in skin by irradiation of 7-dehydrocholesterol (intermediate of cholesterol biosynthesis)


Molecular structure similar to steroid hormone


Vit D3 (cholecalciferol) produced from precursor 7-dehydrocholesterol


-D3 no biological action


-Converted to 25-hydroxyvitamin D3 in liver


-Circulates to kidney converted to 1(alpha)dihydroxycholecalciferol (regulatory enzyme 1(alpha)hydroxylase - stimulated w/ low Ca+ diets)

Vit D Cont

Role in regulating calcium


-Intestine: increases permeability of the entire SI to Ca+(Absence of Vit D only 10-15% of dietary calcium is absorbed - w/ Vit D acting at its receptor increases efficiency to 30-40%)


Bone: mobilization of Ca+


Kidney: increased reabsorption of phosphorus and possibly calcium - inhibits renin synthesis


Muscle: increased muscle tone and contraction thru Ca+ flux


-Skeletal muscle has VitD Rt; Deficiency causes muscle weakness; Increases myocardial contractility


Immune system


-Immunogenic response up regulates VitD synthesis and upregulation of cathelicidin (Peptide capable of destroying infectious agents-TB and others; Low blood levels of VitD, prevent this response)

Pregnancy and lactation

Ca+ demanding states


Prolactin


-Increased expression of Ca+ channels in the gut (Increased Ca+ absorption)


-Increased expression of 1(alpha)hydroxylase genes (Increased synthesis of active VitD)

Mechanism of steroid action: nuclear receptor

Membrane bound receptor Rapid response - occurring in minutes


*rapid intestinal absorption of Ca


*Opening voltage gated Ca+ ad Cl- channels in osteoblasts


VitD Rt has been identified in 30 different tissues/organs


Directly or indirectly Vit D controls more than 200 genes including genes that regulate cell proliferation, differentiation, apoptosis, and angiogenesis

Pathology

PTH necessary for life


Hypocalcemia: convulsion, tetany, death


Bone disease in children- deformity of bones in ankles, knees, and wrists

Pathology


Vit D sensitive deficiency

Deficiency of exposure of skin to sunlight


More common in pigmented skin


No longer common


-Irradiation of food


-Fortified food products - US

Pathology of PTH


Hyposecretion

Hyposecretion of Parathormone


-Ca+ sensor


-Decreased synthesis


Problem w/ PTH receptor


-Gs-alpha subunit - failure to increase cAMP (Active hormones acts on osteoclast to stimulate bone resorption)

Pathology of PTH


Hypercalcemia

Neoplasia of the parathyroid


Overactivity of the parathyroid for unknown reasons


Peripheral defects in PTH action


-Results in hypocalcemia (Stimulates parathyroid chief cell activity)

Vitamin Deficiency

Lack of bone pathology may not indicate "adequate" Vit D


Subclinical Vit D deficiency is prevalent in infants, children, and adolescents in US


- Decrease in UV exposure, Northern latitude, Winter season, Dark skin, Breast milk, Lack of Vit D intake


Implication for future health


Sun Exposure


-Exposure in bathing suit at solar noon for 30 min (20,000 IU of Vit D)



Vitamin Deficiency


Auto-immune conditions

Asthma


Type I diabetes


-2000 IU D/d during 1st yr of life reduced risk of development by 80%


-VitD deficiency increased risk by 200%)


MS


-Season of birth (reflection of UV exposure)


Cancer


-Latitude gradients exists for some malignancies (Hodgkin's, colon, pancreatic, prostate, ovarian, breast cancer)


Obesity and Type II diabetes


Cardiovascular disease

Dairy Cows

10L colostrum requires 23g of Ca (9x the total plasma pool)


40L of milk requires 56g of Ca


Plasma pool comes from diet and bone stores


At parturition a dairy cow must bring in >30g Ca into the plasma pool daily

Milk fever

Occurs at the onset of location


Due to a severe drop in blood Ca (concentration of Ca in milk 12x blood)


Stimulates bone turn over before parturition


-Feed Ca deficient diet

Laying hens

Average egg shell contains 2.3g Ca


250 eggs/year = 580g Ca per year


An average hen weighs 1367g


During shell formation the urerine cells secrete a supersaturated fluid into the shell gland


PTH oscillate during the egg cycle and may regulate shell formation