BIOCHEMISTRY OF HORMONES

SAMINA HYDER HAQ Ph.D

 Assessment
CAT 1=20 Marks
CAT 2 = 20 Marks
Home work assignment = 10 Marks
QUIZ = 10 Marks
Final = 40 Marks

Total = 100 Marks

Recommended Books
Essential Endocrinology and Diabetes
(2007)Richard IG Holt and Neil A Hanley.
Principles of Biochemistry by Smith et al.
Objective
Contrast the terms endocrine, paracrine, and autocrine.
Define the terms hormone, target cell, and receptor.
Understand the major differences in mechanisms of action of peptides
and steroid and thyroid hormones.
Compare and contrast hormone actions exerted via plasma
membrane receptors with those mediated via intracellular receptors.
Understand the role of hormone-binding proteins.
Understand the feedback control mechanisms of hormone secretion.
Explain the effects of secretion, degradation, and excretion on plasma
hormone concentrations.
Understand the basis of hormone measurements (eg,
radioimmunoassay, immunometric assay) and their interpretation.
Introduction
The function of the endocrine system is to coordinate
and integrate cellular activity within the whole body by
regulating cellular and organ function throughout life and
maintaining homeostasis. Homeostasis, or the
maintenance of a constant internal environment, is critical
to ensuring appropriate cellular function.
Function of Endocrine system
Regulation of sodium and water balance and control of
blood volume and pressure
Regulation of calcium and phosphate balance to preserve
extracellular fluid concentrations required for cell
membrane integrity and intracellular signaling
Regulation of energy balance and control of fuel
mobilization, utilization, and storage to ensure that
cellular metabolic demands are met
Coordination of the host hemodynamic and metabolic
counterregulatory responses to stress
Regulation of reproduction, development, growth, and
senescence
Hormone signaling
 Hormone chemistry and Mechanism of
action
Protein or Peptide Hormones
Protein or peptide hormones constitute the majority of hormones.
These are molecules ranging from 3 to 200 amino acid residues.
They are synthesized as pre- prohormones and undergo post-
translational processing. They are stored in secretory granules
before being released by exocytosis .
Steroid Hormones
Steroid hormones are derived from cholesterol and are synthesized in
the adrenal cortex, gonads, and placenta.Vitamin D and its
metabolites are also considered steroid hormones.
Amino AcidDerived Hormones
Amino acidderived hormones are synthesized from the amino acid
tyrosine and include the catecholamines norepinephrine,
epinephrine, and dopamine; as well as the thyroid hormones, derived
from the combination of 2 iodinated tyrosine amino acid residues
 Hormone Transport
Hormones released into the circulation can circulate either
freely or bound to carrier proteins, also known as binding
proteins.
The binding proteins serve as a reservoir for the hormone
and prolong the hormone's half-life, the time during which
the concentration of a hormone decreases to 50% of its
initial concentration.
The free or unbound hormone is the active form of the
hormone, which binds to the specific hormone receptor.
Thus, hormone binding to its carrier protein serves to
regulate the activity of the hormone by determining how
much hormone is free to exert a biologic action. Most
carrier proteins are globulins and are synthesized in the
liver..
 Metabolic Clearance of Hormones
Removal of hormones from the circulation is also known as the
metabolic clearance rate is the volume of plasma cleared of
the hormone per unit of time. Hormones are removed from the
circulation through various mechanisms.
1. Hormones can be inactivated in the liver through Phase I
(hydroxylation or oxidation) and/or
2. Phase II (glucuronidation, sulfation, or reduction with
glutathione) reactions, and then excreted by the liver or the
kidney.
3. Hormones can be degraded at their target cell through
internalization of the hormone-receptor complex followed by
lysosomal degradation of the hormone.
4. A small fraction of total hormone production is excreted
intact in the urine and feces
 Hormone Cellular effect
The biologic response to hormones is elicited through binding to
hormone-specific receptors at the target organ. Hormones circulate
in very low concentrations (107 to 1012 M), so the receptor must
have high affinity and specificity for the hormone to produce a
biologic response.
Abnormal endocrine function is the result of either excess or
deficiency in hormone action. This can result from abnormal
production of a given hormone (either in excess or in insufficient
amounts) or from decreased receptor number or function.
Hormone-receptor agonists and antagonists are widely used
clinically to restore endocrine function in patients with hormone
deficiency or excess.
Hormone-receptor agonists are molecules that bind the hormone
receptor and produce a biologic effect similar to that elicited by the
hormone. Hormone-receptor antagonists are molecules that bind to
the hormone receptor and inhibit the biologic effects of a particular
hormone
Hormone Signaling
 Control of hormone release
Three general mechanisms can be identified as common
regulators of hormone release.

1. Neural Control
2. Hormone Control
3. Nutrients or ion Control
Neural control
Hormone control
Nutrients Ion Regulator
Hypothalamus Pituitary Axis

Most feedback loops run through this axis

HPA mediates growth, metabolism, stress response,
reproduction.
is secondarily in charge of almost everything else
Hypothalamus Connection to pituitary
Neuronal to POSTERIOR PITUITARY
Endocrine to ANTERIOR PITUITARY
RH = Pituitary releasing hormones
RIH = Pituitary release inhibiting hormones
Neurosecretary cells in hypothalamus
Nuclei synthesize and
secrete hormones
Neuronal connection
to POSTERIOR
pituitary
Antidiuretic Hormone
(ADH), Oxyt
Hormones synthesized in the Secretion of Posterior pituitary
hypothalamus are transported down
the axons to the endings in the
posterior pituitary
Hormones are stored in vesicles in the
posterior pituitary until release into the
circulation
Main hormones are
Oxytocin
Target = smooth ms. Uterus and Breast
(&brain)
Function = labor and delivery, milk
ejection,(pair bonding)
ADH (Vasopressin AVP)
Target = kidneys
Function = water reabsorpti
 Anterior pituitary hormones
The anterior pituitary is composed of
groups of epithelial cells surrounded
MSH ,ACTH
by wide capillaries called sinusoids.
LH.FSH
Different populations of cells
produce different hormones.
Anterior pituitary
Corticotropes - ACTH and MS
Lactotropes - Prolactin
Somatotropes - GH
TSH PRL
Thyrotropes - Thyrotropin GH capillaries

Gonadotropes - FSH, LH
Anterior pituitary hormone (1. Growth hormone)

GH is produced and stored in

somatotrophs in the anterior pituitary.
The production of GH is pulsatile, mainly
nocturnal, and is controlled by GHRH and +
somatostatin.
Circulating levels of GH increase during
childhood, peak during puberty, and fall IG
with aging. F

GH stimulates lipolysis, amino acid

Growth and cellular
transport into cells, and protein synthesis. differentiation in bone, muscles
GH stimulates the production of IGF-I, and adipose tissues
which is responsible for many of the
activities attributed to GH.
Anterior pituitary hormone(2.LH,FSH)
The gonadotropic hormones LH and FSH are
synthesized and secreted by gonadotrophs of
Testes FSH
the anterior pituitary in response to LH
stimulation by gonadotropin-releasing
hormone (GnRH). FSH
LH
FSH and LH exert their physiologic effects on
multiple cells of the reproductive system by
binding to Gs' proteincoupled receptors and
activation of adenylate cyclase. Among the testosterone
target cells for gonadotropins are ovarian Ovary
Inhibin
granulosa cells, theca interna cells, testicular
Sertoli cells, and Leydig cells. The physiologic estrogen Progestron
responses produced by the gonadotropins
include stimulation of sex hormone synthesis
(steroidogenesis), spermatogenesis, Effect on brain ,vascular
tissues and behavior.
folliculogenesis, and ovulation. Therefore, their
central role is the control of reproductive
function in both males and females.
Anterior pituitary hormone (3.Prolactin)

The main physiologic effects of

prolactin are stimulation of growth and
development of the mammary gland,
synthesis of milk, and maintenance of
milk secretion
Prolactin modulates immune cell
function through endocrine
mechanisms.
prolactin can act as a cytokine because
it is released by cells of the immune
system and regulates the lymphocyte
responses by both paracrine and
autocrine mechanisms.
Anterior pituitary hormone(4.TSH)

Thyroid-stimulating hormone (TSH)

regulates the thyroid gland
TSH acts on the thyroid gland to stimulate the
release of thyroid hormones (Thyroxine, T4,
Tri-iodothyronine, T3.
The thyroid hormones play an important role in
controlling carbohydrate and fat metabolism,
and basal metabolic rate.
 Anterior pituitary (5.ACTH)
Adrenocorticotrophic hormone
(ACTH) controls hormone
secretion from the adrenal cortex
ACTH acts on the adrenal
cortex to stimulate the release
of glucocorticoids (mainly ACTH
cortisol) and adrenal
androgens. adrenal
cortex
Cortisol controls the
Adrenal cortex hormones
metabolism of carbohydrates,
fats and proteins, inflammatory
and immune responses, and Metabolism, immune system,
responses to stress. stress responses, testosterone
and oestrogen
 Anterior Pituitary (6. MSH)
MSH acts on melanocytes in the
epidermis of the skin to stimulate
the secretion of melanin

Melanin controls pigmentation in the skin. MSH