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