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Presentation topic
Steroid Hormone and nuclear receptors signaling
Present by
naseem
bhurgri
WHAT IS HORMONE
a regulatory substance produced in an
organism and transported in tissue fluids such
as blood or sap to stimulate specific cells or
tissues into action
TYPES OF HORMONES
Amine Hormone
Peptide/protein hormones
Steroid hormones
AMINE HORMONES
Hormones derived from the amino acid tyrosine.
These include epinephrine, norepinephrine and thyroid hormone.
Epinephrine and norepinephrine are produced by the adrenal medulla –water soluble
Thyroid hormone is
produced by the
thyroid gland –lipid
soluble
PEPTIDE/PROTEIN HORMONES
Range from 3 amino acids tohundreds of amino acids in size.Often produced as larger molecularweight precursors that areproteolytically cleaved to the activeform of the hormone.Peptide/protein hormones are watersoluble.Comprise the largest number ofhormones– perhaps in thousands
STEROID HORMONES
All steroid hormonesare derived fromcholesterol and differonly in the ringstructure and sidechains attached to it.All steroid hormonesare lipid soluble1,25-dihydroxyVitamin D3 is alsoderived fromcholesterol and is lipidsoluble
STEROID HORMONES
Steroids are lipid soluble and thus are freely permeable to membranes so are not stored in cells
Are not packaged, but synthesized and immediately released
Are all derived from the same parent compound: Cholesterol
Enzymes which produce steroid hormones from cholesterol are located in mitochondria and smooth ER
STEROID HORMONES
Steroid hormones are not water soluble so have to be carried in the blood complexed to specific binding globulins.
Corticosteroid binding globulin carries cortisol Sex steroid binding globulin carries testosterone and estradiol In some cases a steroid is secreted by one cell and is converted
to the active steroid by the target cell: an example is androgen which secreted by the gonad and converted into estrogen in the brain
TYPES OF STEROID HORMONES
Glucocorticoids
Mineralocorticoids
Progestogens
Estrogens
Androgens
glucocorticoid
•a corticosteroid which
is involved with
maintaining the salt
balance in the body,
such as aldosterone
a male sex hormone, such as
testosterone
OESTROGEN
•any of a group of steroid hormones which
promote the development and maintenance of
female characteristics of the body. Such
hormones are also produced artificially for use
in oral contraceptives or to treat menopausal
and menstrual disorders
PROGESTOGENS
•a natural or synthetic steroid hormone,
such as progesterone, that maintains
pregnancy and prevents further ovulation
during pregnancy
HOW DOES THE SYNTHESIS OF STEROIDS DIFFER FROM THAT OF PEPTIDE HORMONES?
• While peptide hormones are encoded by specific genes, steroid
hormones are synthesized from the enzymatic modification of
cholesterol.
• Thus, there is no gene which encodes aldosterone, for example.
• As a result:
- There are far fewer different types of steroid hormones than
peptide hormones.
- Steroid structures are the same from species to species
- The regulation of steroidogenesis involves control of the
enzymes which modify cholesterol into the steroid hormone of
interest.
THE ROLE OF CHOLESTEROL IN STEROID SYNTHESIS
• The first enzymatic step in the production of ANY steroid
hormone begins with enzymatic modification of cholesterol
STEROID HORMONES: MOLECULAR ACTION
“
”
FORMATION OF STEROID HORMONES
Sources of steroid hormone formation in the body can be divided
into two types
One source is the endocrine glands.
In women, they include the adrenals, ovaries, and placenta, which is an incomplete
endocrine gland. In men, the endocrine glands include the adrenals and testes.
A second source of steroid hormones in the body is peripheral tissues. These are
nonendocrine tissues such as the liver, intestine, fat, skin, kidneys, and brain.
STEROID HORMONE BIOSYNTHESIS IN THE OVARIES AND TESTES
STEROID HORMONE BIOSYNTHESIS IN THE ADRENALS
STEROID HORMONE BIOSYNTHESIS IN THE PLACENTA
NUCLEAR RECEPTORS SIGNALING OF STEROID
• These hormones act through binding to specific intracellular
receptor proteins that function as both signal transducers and
transcription factors to modulate expression of target genes
• Molecular cloning has revealed 48 steroid hormone and nuclear
receptor genes in humans.
MEMBERS OF THE STEROID HORMONE RECEPTOR GENE SUPERFAMILY IN MAMMALIAN TISSUES
ERα
ERβ
HAR
PR
GR
MR
VDR
TRs
hTR
RAR
alpha
Beta
gama
DAX
RTR
RZR
GENERAL MODEL OF STEROID HORMONE RECEPTOR MECHANISM OF ACTI0N
FUNCTIONS OF STEROID HORMONES
• Steroid hormones play important roles in:
- carbohydrate regulation (glucocorticoids)
- mineral balance (mineralocorticoids)
- reproductive functions (gonadal steroids)
FUNCTIONS OF STEROID HORMONES
• Steroids also play roles in inflammatory responses, stress
responses, bone metabolism, cardiovascular fitness, behavior,
cognition, and mood.
FUNCTIONS OF HORMONES DERIVED FROM CHOLESTEROL
FUNCTIONS OF HORMONES DERIVED FROM CHOLESTEROL
REFERNCES
• Stocco DM, Clark BJ: The role of the steroidogenic acute regulatory
protein in steroidogenesis. Steroids 62:29-36, 1997
• Papadopoulos V, Amri H, Boujrad N, et al: Peripheral benzodiazepine
receptor in cholesterol transport and steroidogenesis. Steroids
62:21-28, 19
• Chung B-C, Picado-Leonard J, Haniu M: Cytochrome P450c17 (steroid
17α-hydroxylase/17,20 lyase): Cloning of human adrenal and testis
cDNAs indicates the same gene is expressed in both tissues. Proc
Natl Acad Sci USA 84:407-411, 1987
REFERENCES
• Kagimoto M, Winter JS, Kagimoto K, et al: Structural
characterization of normal and mutant human steroid 17-
alpha-hydroxylase genes: Molecular basis of one example of
combiend 17-alpha-hydroxylase/17,20 lyase deficiency. Mol
Endocrinol 2:564-570, 1988
• Lorence MC, Corbin CJ, Kamimura N, et al: Structural analysis of
the gene encoding human 3 beta-hydroxysteroid
dehydrogenase/delta 5-4-isomerase. Mol Endocrinol 4:1850-
1855, 1990