Creado por Marissa Alvarez
hace alrededor de 5 años
|
||
0 | ||
0 | ||
0 | ||
0 | ||
0 |
There are no comments, be the first and leave one below:
Endocrine: Growth
Objectives
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
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
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
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
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
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
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 ____
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
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
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 (____)
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 (____)
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 ___
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
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
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 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
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
(______)
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)
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)
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