HORMONAL

REGULATION
OF
GROWTH
PUBERTY &
DR. RAHMA TRILIANA, S.KED., M.KES., PHD
30 MARET 2017
 HORMONES
Derived from a Greek word Horman
or Horme meaning to impel or to
urge on or to set in motion
A regulatory substance (Chemical
messenger) produced by organism,
transported via blood stream to stimulate
specific cells or tissue within organism
Specific actions elicited through a
RECEPTOR Lock & Key or Induced fit
binding to produce intracellular signaling
Genomic or Non Genomic activities
Hormones activity is modulated via
feedback
mechanisms.
Hormones are mean to
communicate
BASIC
CONCEPT ORGANS/CELLS
SYTHESIS

STIMULANTS
PROCESS ENDOCYTOSIS

RECEPTOR BINDING
SECOND MESSENGER
GENE REGULATION

ACTIVITIES
PHYSIOLOGICAL EFFECT

INHIBITORS
DOWN
REGULATION
 BASIC
STRUCTURE OF
HORMONES
Hormones
Metabolism
 Interrelation of
Hormones
and
Neurotransmitters
Control of
Hormones

Actions
Hormonal
Aspects
of Growth
 GROW
TH
Synonyms: development, maturation, growing, sprouting,
blooming.
Definition:
the process of increasing in physical size.
something that has grown or is growing.
a positive change in size, and/o maturation over a period
of time.
Growth quantity can be:
Physical (e.g., growth in height, growth in an amount)
Abstract (e.g., becoming more complex, or more mature)
Growth in Human Term can mean:
Cell growth
Physical development
Psychology development
Personal development / Personal growth
 Factors Influencing

Growth
GENETIC
Influenced final height heritable
GEND
pattern
ERDetermine postnatal increase
in length
SOCIO-
Give intrinsic rate of change in
growth poor nutrition, low hygiene, & bad
Poverty
ECONOMIC
health status
Geographic location
NUTRITI
Socioeconomic status & nutrition > genetic
ONMalnutrition,
endowments Micro or macro nutritional deficiencies, voluntary or
not effects
growth.
Due to GH receptors or postreceptor defects in GH action IGF-
PSYCHOLO
I and serum IGF-I
Intrafamilial dynamics, psychologic stress, psychiatric disease
GIC
alter endocrine function Psychosocial dwarfism
Feeding problems in children (inexperienced parents, poor child-
parent interactions,
maternal deprivation),
CHRONIC
Deliberate starvation
Shifted nutrient
DISEASE usageof&children
Changed (child abuse)activity i,e, thyroid
endocrine
dysfunction, GH,
glucocorticoid excess, celiac disease etc.
 Intrauterine
Growth
Single fertilized cell differentiate into > 200 cell types,
increased length by 5000X, surface area by 6 106 X, &
weight by 6 1012 X
Fetal growth is dependent on 1) Adequate oxygen, 2)
nutrition and well orchestrated actions of growth factors
Genetic factors is important in early gestation, while
Maternal environment is
important in late gestation.
Small for gestational age (SGA) = birth weight below 2
SD of mean OR 5th
percentile for birth weight OR birth weight < 2500 g (in
USA) 20% of SGA
infants remain short as children and adults
Intrauterine growth retardation / intrauterine growth
restriction (IUGR) is decreased intrauterine growth velocity
can result in SGA.
 POSTNATAL
GROWTH
Follows a characteristic pattern in normal children
Highest postnatal growth rate is after birth, slower in mid
childhood
Brief growth spurts in childhood
Infant - childhood growth spurt 1/2 years - 3 years
Mid childhood growth spurt 6 1/2years - 7 years
adiposity rebound weight gain & body mass index (BMI) in
early childhood
risk factor for obesity
Childhood growth plateau
After Plateau pubertal growth spurt second peak of growth
velocity
epiphyses fuse & growth ceases
Catch-Up Growth
Correction of temporary growth-retarding disorders high growth
rate catch-up
Short-lived then return to normal average growth rate.
 MEASUREMENT OF
GROWTH
Using anthropometric assessment
Assess length (< 2 yr old), height, weight
Mid-Upper Arm or head circumference
Gestational age
Arm span, knee height (knemometer),
elbow breadth
Using Growth Rate Summary or
growth indices
Head circ., weight, height for age
Weight for height
Using Body mass Index
Assessing body composition
Triceps or abdominal Fat-fold, Skin fold
thickness
Percentage of Body fat, muscle mass and
bone mass
Waist to hip ratio
Hormonal Regulation of
Growth
Pituitary growth hormone
Insulin and Insulin like Growth
factor / IGF-1
Thyroid hormone
Sex hormones (testosterone,
estrogen)
Pituitary gonadotropic Hormones
Prolactin
* Role in puberty
 Growth
Hormones
Secreted by SOMATOTROPHS GH-secreting cells,
acidophilic, in lateral portions of the anterior lobe, 50% of
the adenohypophysial cells are somatotroph
GH / somatotropin 191-amino-acid polypeptide
hormone (MW 21,500 Da)
Precursor peptide = preGH (MW 28,000 Da) also secreted
no physiologic
significance.
Function is in the adult is unclear, In children important for
growth
Promotion of linear growth mediated by insulin-like growth
factor 1 (IGF-I; or somatomedin C).
Secreted in small bursts of activity and regulated by GHRH
and somatostatin
(GH-inhibiting hormone) episodic pattern of GH secretion.
GH being species-specific GH must come from human
glands to be active in other man GH for hormonal treatment
obtained from autopsy. Now using recombinant DNA.
Signaling of
Growth
Hormone &
GHR
 FACTOR
EFFECTING GH SECRETION
 Thyroid
Hormones
Secreted by Thyroid gland in the neck
Important for normal growth although Act IN-
directly to stimulate growth by improving
cells development & function
Temporary insufficiency may be normal, if
untreated can suffer permanent mental
retardation, cretinism, short stature, and
poor lower limb growth
Hypothalamic pituitary thyroid axis.
The role of individual thyroid hormone
receptor (TR) isoforms in each
compartment is summarized on the
right side of the figure.
 FOUR STAGES OF
THYROID HORMONE
1.Synthesis of Thyroglobulin.
SYNTHESIS
2.The Uptake of Circulating Iodide
Thyroid follicular cells by a membrane
transport protein,
Na/I symporter (NIS). Serum I regulate thyroid
function.
3.Oxidation of Iodide by Thyroid
Peroxidase Transported to
cavity by an anion transporter (pendrin).
4.Iodination of Tyrosine Residues
Catalyzed by thyroid peroxidase MIT & DIT
Coupling produces hormones T3 & T4
larger thyroglobulin molecule.
 THYROID

METABOLISM
THYROID
HORMONES

ACTIVITY
 Physiologic Effects of Thyroid
Hormones
Target Effect Mechanism
I nnccrreeaasseedd nprumopoberrtioonf of
Heart Chronotrop adrenergic receptors
ic
Enhanced responses to
Inotropic
circulating catecholamines
myosin heavy chain (w/ ATPase
activity)
Adipose tissue Catabolic Stimulated lipolysis
Muscle Catabolic Increased protein breakdown
Bone Development Promote N growth & skeletal
al development
Nervous Development Promote normal brain development
system al
Gut Metabolic Increased rate of carbohydrate
absorption
Lipoprotein Metabolic Formation of LDL receptors
Other Calorigenic Stimulated O2 consumption by
metabo- lically active tissues
(except: testes, lymph nodes,
uterus, spleen, anterior pituitary)
Increased metabolic rate
SEX STEROIDS
Gonadal sex steroids exert an important influence on
the pubertal growth spurt, whereas absence of
these fa-tors is not of major importance in
prepubertal growth.
Gonadal and adrenal sex steroids in excess can cause a
sharp increase in growth rate as well as the premature
appearance and progression of secondary sexual fea-
tures. If unabated, increased sex steroids mediated by
estrogen will cause advancement of skeletal age, prema-
ture epiphysial fusion, and short adult stature.
The pubertal rise in gonadal steroids exerts direct and
indirect effects on IGF-I production. Estrogen (secreted
or aromatized from testosterone) directly stimulates the
production of IGF-I from cartilage and also increases GH
secretion, which stimulates IGF-I production indirectly.
Both actions appear important in the pubertal growth
spurt
Signaling
VIA the
Steroid
Receptor
Complex
GLUCOCORTICOIDS
Endogenous or exogenous glucocorticoids in excess
quickly stop growth;
this effect occurs more quickly than weight gain.
The absence of glucocorticoids has little effect on
growth if the individual is clinically well in other
respects (ie, if hypotension and hypoglycemia are
absent).
PUBER
TY
 Male Sequence of
Secondary
Sexual Development
Female Sequence of
Secondary
Sexual Development
Hormone
Level in
Stages of
Puberty
SEX SPECIFIC
HORMONAL LEVEL
THROUGHOUT LIFE
 TESTOSTERONE LEVELS THROUGHOUT
LIFE

Testosterone regulates spermatogenesis, male sexual

appearance & libido