• Hormones may be defined as—‘substances secreted by the endocrine, or ductless glands that essentially serve to integrate various metabolic processes’.
• It is observe that hormones do represent a widely diverse category of compounds, for instance ;
• Amino acid derivatives e.g., thyroxine, epinephnine ;
• Steroids-e.g., testosterone, progesterone, cortisone, hydrocortisone ;
• Polypeptides/proteins-e.g., corticotropin, calcitonin, insulin ;
• While, steroid hormones are solely responsible for the reproductive system, they are also the causative substances for the growth and development of cancers related to breast, prostate and uterine.
STEROIDAL HORMONES
• Steroid hormones and related products represent one of the most widely used classes of therapeutic agents, These drugs are used primarily in birth control, hormone-replacement therapy (HRT), inflammatory conditions, and cancer treatment. Most of these agents are chemically based on a common structural backbone, the steroid backbone.
• Five general groups of steroid hormones are common: estrogens, progestins, androgens, glucocorticoids and mineralocorticoids
Fig: Basic steroid structure
Functional Classification of Steroids
Ö Anabolic Steroids
- Interact with androgen receptor; enhance muscle mass/athlete’s performance; male sex hormones
Ö Glucocorticoids
- regulate metabolism and immune function; anti-inflammatory activity Ö Mineralocorticoids
- maintain blood volume and renal excretion Ö Progestins
- Development of female sex organs and characteristics Ö Phytosteroids
- Plant steroids Ö Ergosteroids
- Steroids of the fungi; vitamin D related
STEROID CHEMISTRY
• Steroid molecules possess a common chemical skeleton of four fused rings, consisting of three six-membered rings and a five-membered ring.
• Chemically, this hydrocarbon scaffold is a cyclo-pentano-perhydro-phenanthrene, describing the three rings of phenanthrene (rings A, B, and C) and the cyclopentane ring (ring D in steroids.
• the phenanthrene ring system is completely saturated (hydrogenated). This steroid scaffold contains 17 carbon atoms.
• Additional carbon atoms on steroids include angular methyl groups attached to C13 and C10 and alkyl substituents on C17.
• The stereochemistry of the rings and the substituents on the steroid scaffold
markedly affects the biologic activity of a given class of steroids
• The stereochemistry of the H at C5 is always indicated in the name.
• Changing the stereochemistry of any of the ring juncture or backbone carbons greatly changes the shape of the steroid, as seen in the examples of 5α,8α-androstane & 5β-androstane
• Many of the biologically important steroids contain a carbon-carbon
double bond between positions 4 and 5 or 5 and 6, and consequently
there is no cis or trans relationship between rings A and B.
Structures of common steroids:
STEROID BIOSYNTHESIS
• Steroid hormones in mammals are
biosynthesized from cholesterol, which in
turn is made in vivo from acetyl coenzyme
A (acetyl-CoA) via the mevalonate
pathway. Although humans do obtain
approximately 300 mg of cholesterol per
day in their diets, a greater amount (about
1g) is biosynthesized per day.
Cholesterol
Progestins
Glucocorticoids Androgens
Mineralocorticoids Estrogens
Progestins Are the Biosynthetic
Precursors of the All Other Steroid
Hormones
Pregnenolone ( C-21 )
produced directly from cholesterol, the
precursor molecule for all C
18, C
19and C
21steroids
•
A progestin, produced directly from pregnenolone.•
Secreted from the corpus luteum.•
Maintains (with estradiol) the uterine endometrium for implantation.•
Differentiation factor for mammalian glands.Progesterone ( C-21 )
•
Female: regulates gonadotrope secretion in ovarian cycle.•
Maintains (with progesterone) uterine endometrium.•
Differentiation of mammalian gland.•
Responsible for secondary female sex characteristics.•
Male: negative feedback inhibitor of Leydig cell synthesis of testosterone.Estradiol ( C-18 )
•
After conversion to dihydrotestosterone, production of sperm proteins in Sertoli cells.•
Responsible for secondary male sex characteristics.•
Produced from progesterone.Testosterone ( C-19 )
Dehydroepiandrosterone
•
Week androgen, which can be converted to estrogen.•
Various protective effects. It may play a role in the aging process.•
Regulates NAD+ coenzymes.Cortisol ( C-21 )
•
Dominant glucocorticoid in humans,synthesized from progesterone in the zona fasciculata of the adrenal cortex.
•
Stress adaptation through various cellular phenotypic expression, stress adaptation.•
Slight elevation of liver glycogen. Numerous effects on the immune system, killing effect on certain T cells in high doses.•
Na+ uptake in epithelia lumen.Aldosterone ( C-21 )
•
The principal mineralocorticoid.•
Produced from progesterone in the zona glomerulosa of adrenal cortex.•
Causes sodium ion uptake via conductance channel.•
Occures in high levels during stress.Rises blood pressure and fluid volume.
O
O OH HO
HO
A B
C D
Structure-Activity Relationship
Essential for activity
1 2
3
4
5
9
10 19
18
11 13
14
16 17 1, 2 Double bond improve carbohydrate
metabolism to Na+ retention
-CH3 increase glucocorticoid activity
6
-CH3 in Cortisol increase all activities
-CH3 in Prednisolone increase antiinflammatory activity
&Decrease Na+ retaining activity
9-Fluoro increase all activities F Br Cl
Essential for antiinflammatory activity
& carbohydrate regulatory activity
12
-F increase all activities if no OH at C-17
-F with 16dihydroxy--inactive compounds
CH3 or OH eleminate Na+ retention activity Essential for activity
Essential for antiinflammatory activity Ether & esters increase
antiinflammatory &
glucocorticoid activities 21
Halogen & halomethylene greatly increase Topical antiinflammatory activity
