Lecture 3 - Endocrine: Growth

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PSIO 743 - Graduate Physiology Karteikarten am Lecture 3 - Endocrine: Growth, erstellt von Marissa Alvarez am 30/10/2019.
Marissa Alvarez
Karteikarten von Marissa Alvarez, aktualisiert more than 1 year ago
Marissa Alvarez
Erstellt von Marissa Alvarez vor etwa 5 Jahre
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Endocrine: Growth Objectives •Define the periods of growth and their characteristics •Understand the actions and the mechanisms of action for GH on bone and soft tissues •Role of IGF-1 (and IGF-II) •Describe the factors that control GH secretion •Examine the role of sex steroids •Define and understand the clinical symptoms associated with abnormalities in GH secretion
Endocrine Control of Growth GROWTH –Under influence of growth hormone: •Net synthesis of ___ •↑___ of the long bones •↑ size and number of ___ in soft tissues -Factors other than GH affect growth: •Genetics ->Inheritance ->Abnormalities can cause various developmental defects •Diet ->Malnourishment -> ↓ growth potential (__% brain development in first 2 years) ->Excess = ____, not growth •Freedom from disease and stressful environment ->Prolonged stress-induced secretion of ___ -> stunted growth (through protein break-down, ↓ __ ___ growth, inhibiting __ secretion) –Normal levels of growth-influencing hormones: •Thyroid hormone •Insulin •Sex hormones proteins Length cells 70% OBESITY cortisol long bone GH
Growth Not continuous: –FETAL growth •___ hormones •Genetic/environmental factors determine ___ at birth •GH ___ involved –CHILDREN •Postnatal growth spurt: –1st _ years –After -> rate linearly ___ until puberty •Pubertal growth spurt (11 yrs for females, 13 yrs for males): –Marked ____ in linear growth –Cause not well-understood –Genetic/hormonal factors » _ androgens -> protein synthesis and bone growth »T from testes, adrenal androgens in ___ *BOTH _ & __ -> halt bone growth at end of puberty Placental size NOT 2 declines acceleration ↑ females T (testosterone) & E2 (estradiol)
Metabolic Effects of GH NOT Related to Growth -GH is the MOST abundant ___ hormone secreted, even in adults, suggesting actions in ___ to growth -Exerts actions by binding ____ to target tissues -During prolonged FASTING or if energy requirements EXCEED available glucose stores: ->Adipose »Breakdown triglycerides -> ↑ [fatty acid]blood ->Skeletal muscles »↑ use of __ __ for fuel (glucose sparing) »_ glucose uptake [↑ [glucose]blood = conserved for glucose-dependent tissues (__ , __)] –>Liver » _ glucose output [↑ [glucose]blood = conserved for glucose-dependent tissues (__ , __)] ->Also stimulates ___ synthesis -> _ [amino acid]blood »May or may not be a direct action anterior pituitary (AP) addition DIRECTLY ↑ fatty acids ↓ heart, brain ↑ protein ↓
Growth Hormone Does NOT act ___ to exert effects on growth –Actions mediated by insulin-like growth factors (__ & __) •Structurally and functionally similar to insulin •Produced by many tissues •Have endocrine, paracrine, and autocrine actions •Act via __ ___ pathway directly IGF-I & IGF-II tyrosine kinase
IGF-I –70 a.a. protein, synthesis stimulated by __ –Mediates GH’s growth-___ actions –Major source = ___ (released into blood) •Also produced locally by most other tissues (___) –> NOT released to blood –Is paracrine secretion a major factor during postnatal growth (first _ years) period? »Circulating [GH] and [IGF-I] are __ during this time –Control of PRODUCTION (other than by GH): •Nutrition: [↓ intake -> _ IGF-I (but _ GH)] •Age-related factors: ( _IGF-I accompanies _ GH at puberty -> pubertal growth spurt) •Tissue-specific stimulatory factors: –FSH/LH & sex steroids -> ↑ IGF-I within reproductive organs GH promoting Liver paracrine 2 low ↓ ↑ ↑ ↑
Growth Hormone IGF-II –Production NOT influenced by __ –Major source = ___ PRIMARY ROLE: •During FETAL development: –Receptors expressed very __ in development (in contrast, IGF-I receptors not expressed until later in fetal life) »Found in _____ cells (develops into the fetal portion of placenta) –Stimulates ___ growth –Stimulates both pre- and post-implantation embryonic growth In NEWBORNS: –IGF-II _, while IGF-I _ •Secreted during adulthood, but UNKNOWN role –Patients with tumors that secrete IGF-II develop ____ »Binds to insulin receptors @ ___ -67 a.a. -62% homology with IGF-1 -Immunologically ___ than IGF-1 GH liver early trophoblast placental ↓ ↑ hypoglycemia (low blood sugar) liver different
Growth Hormone -GH (acting through __) stimulates growth in soft tissues and skeleton SOFT TISSUE –Hyperplasia (_ # cells) •↑ cell division •↓ apoptosis –Hypertrophy (↑ __ of cells) • _ protein synthesis –↑ amino acid uptake by cell –↑ activity of synthesis machinery »↑ DNA & RNA synthesis »↑ incorporation of amino acids into protein @ ribosome •↓ protein ____ IGF-I ↑ size ↑ degradation
Growth Hormone Effects on Skeletal Growth Effects on bone growth BONE STRUCTURE: ~____~ –Extracellular matrix composed of collagen fibers and semisolid gel »Responsible for tensile ___ of bone –CaPO4 precipitation -> bone ____ »Responsible for resistance to ____ ~____~ –Form bone by secreting osteoid ~_____~ –Dissolve bone tissues »Release minerals to blood •Relevant ANATOMY: –Periosteum »____ tissue surrounding bone –Diaphysis »___ of a long bone »Hollow, central cavity •Contains __ ___ –Epiphysis »“___” at either end of long bone •Where articulations are formed –___ ___ »Cartilaginous growth region b/w diaphysis and epiphysis Osteoid strength hardening compression Osteoblasts ("Blasts Build Bone") Osteoclasts ("Clasts Cut bone") Connective Shaft bone marrow "knob" Epiphyseal plate
Bone Growth Ossification (bone ___) •Thickness: –Addition of new bone to surface of existing bone by osteo___ in the periosteum –Osteo___ along inner surface remove bone to enlarge marrow cavity formation blasts ("osteoBlasts BUILD") clasts ("osteoClasts CUT")
Bone Growth LENGTH –Cartilage at ___ of epiphyseal plate is replaced with __: »Chondrocytes along epiphysis edge of epiphyseal plate multiply (temporary widening of ____ ___) »Older chondrocytes toward diaphysis _____ »Oldest hypertrophied cartilage is ____ »Chondrocytes die due to lack of access to ___ »Osteoclasts ___ away dead cells and calcified matrix »Osteoblasts move in (with blood supply) and ___ bone (____) bottom bone epiphyseal plate hypertrophy calcified nutrients clear build (ossification)
Bone Growth LENGTH –Cartilage at ___ of epiphyseal plate is replaced with __: »Chondrocytes along epiphysis edge of epiphyseal plate multiply (temporary widening of ____ ___) »Older chondrocytes toward diaphysis _____ »Oldest hypertrophied cartilage is ____ »Chondrocytes die due to lack of access to ___ »Osteoclasts ___ away dead cells and calcified matrix »Osteoblasts move in (with blood supply) and ___ bone (____) lacunae canaliculi Osteocytes matrix calcium parathyroid
Bone Growth Role of GH (via IGF-I) •Causes growth in both ___ and ___ • __ proliferation of epiphyseal cartilage • __ osteoblast activity –↑ length of long bones IF epiphyseal plate remains ____ »Sex hormones -> complete ____ (closure) •Normally at ___ length thickness ↑ ↑ cartilaginous ossification puberty
REVIEW: Growth: -Factors affecting growth -Not continuous Growth Hormone: -Direct role in metabolism -Indirect role n growth -IGF-1 vs. IGF-2 GH on soft tissues: -via IGF-1 -hyperplasia & hypertrophy GH & Bone Growth: -cartilage cells (chondrocytes) -osteoclasts -osteoblasts -epiphyseal plate -Laying down of bone @ the epiphyseal plate
Regulation of Secretion –GHRH and GHIH (____) •G-protein coupled receptors, with GHRH ____ and GHIH ____ cAMP •Negative feedback loops involve ____ of stimulatory factors and ____ of inhibitory factors –Factors affecting GH secretion •Displays ____ rhythm Recall that GH promotes ___ conservation for the brain: •Exercise & stress = __ [glucose]blood somatostatin increasing decreasing inhibition stimulation diurnal glucose ↓
GROWTH HORMONE During these extraneous situations: –↓ fat stores & ↑ body proteins • -> change in body composition –Away from ___ deposition –Toward muscle ____ (GH mary meditate effects of exercise) –If ↑protein meal -> _ [amino acid]blood -> _ GH secretion ->protein synthesis –↓ [fatty acid]blood -> _ GH secretion -> mobilizes fat -> ___ [fatty acid]blood –Ghrelin (from ___) -> _ GH secretion •Coordination of growth with nutrient acquisition adipose hypertrophy ↑ ↑ ↑ stabilize stomach ↑
GROWTH HORMONE Summary of regulation –Aimed at adjusting glucose, amino acids, and fatty acids –NO known ___-related signals influence growth hormone secretion •Levels of GH in early childhood, a period of accelerated growth, are ___ to those seen in adulthood •Why don’t soft tissues continue to grow under influence of GH? –GH may only be high enough during deep ___ »Time spent in deep sleep greatest during infancy and ___ with age »Time still spent in deep sleep in adulthood, yet we still ___ grow larger growth similar sleep declines don’t
Growth Hormone DEFICIENCY Causes –Primary: ___ defect (lack __) –Secondary: ___ dysfunction (lack ___) Deficiency in CHILDHOOD: –Dwarfism » ___secretion of GH »Impeded skeletal growth -> short stature »Poorly developed muscles •_ protein synthesis »Excess subcutaneous fat stores •_ fat mobilization –Laron dwarfism »Abnormal ___ receptors •No response to __ •[GH]blood very ___ –GH adequate, but ___ is low (Target cell responsiveness to GH normal, but IGF-1 lacking) »Ex: African pygmies ___secretion during ADULTHOOD: –↓ skeletal muscle mass »↓ strength –↓ bone density »__ osteoblast activity during remodeling –↑ risk for ___ failure Pituitary GH Hypothalamic GHRH Hypo ↓ ↓ GH GH high IGF Hypo ↓ heart
Growth Hormone EXCESS Primary cause: –____ tumor of somatotropes •Symptoms dependent on ___ of onset: ->Childhood: (prior to epiphyseal plate ___) »Rapid growth in height without distortion of body proportions (____) –Post-adolescence: »No more ___ in height »Bones thicken •Extremities & face •Jaws and cheekbones become more ___ »Soft tissue proliferation •Skin, connective tissues »Hands and feet ___ •Fingers and toes thicken ->Disproportionate growth pattern (______) Pituitary (somatotropes produce GH) age closure Gigantism growth prominent enlarge Acromegaly
Other Hormones Essential for Growth Thyroid Hormone: _____ •Not directly responsible for promoting growth •Stunted growth in ___thyroid children (but not opposite effect if hyperthyroid) •Insulin–Deficiency = ___ growth –Excess = excessive growth –Promotes protein synthesis –Structurally resembles __ (so interaction with IGF-I receptor is possible) •Androgens –Effects depend on presence of __ •Stimulate protein synthesis –Linear growth, weight gain, muscle mass ->Eventually, stop growth by promoting epiphyseal plate closure following conversion to ___ •Estrogens –Promote epiphyseal plate ___ •Other “poorly” understood peptide growth factors: –Stimulate mitotic activity in specific tissues (Ex: epidermal growth factor) Permissive hypo blocks IGFs GH estrogen closure
SEX Differences in Growth •Puberty occurs ~ 2 years ___ in girls –Boys have ~ 2 more years of ___ •Average boy is ___ at beginning of the pubertal growth spurt than average girl •Greater ___-induced growth spurt in boys (↑ growth prior to plate closure) •Pubertal estrogen ↑ -> ↓ pubertal growth spurt (____ growth prior to closure) •_____ program brain for masculine GH secretion pattern (↑ cyclic peaks -> ↑ height in males) earlier growth taller androgen Slowing Androgens
REVIEW Regulation of GH secretion: GHRH GHIH (somatostatin) Reytemincinty Exercise Stress Glucose Amino acids Fatty acids Ghrelin GH Disorders: Hyposecretion: Dwarfism (childhood) Laron Dwarfism (receptor insufficiency) Lack of IGF-1 (African Pygmies) Adulthood (minor symptoms) Hypersecretion: Gigantism Acromegaly Other hormones that influence growth: Thyroid, insulin, androgens, estrogens, peptide growth factors
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