Steroids and Their Structure

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Questions and Answers

What is the primary structural characteristic of steroid molecules?

A branched carbon chain structure

Four fused rings forming a hydrocarbon skeleton (correct)

A singular hexagonal ring structure

A linear chain of carbon atoms

Which of the following compounds is considered the parent compound of all steroids?

Acetyl-CoA

Cholesterol (correct)

Cyclopentanoperhydrophenanthrene

Phenanthrene

In the context of steroid nomenclature, groups above the plane of the molecule are said to be in which position?

δ-position

α-position

β-position (correct)

γ-position

Which of the following is NOT a typical use of steroidal drugs?

Antibiotic therapy Signup and view all the answers

What is the structure consisting of three cyclohexane rings and one cyclopentane ring known as?

Steroid backbone Signup and view all the answers

Which factor is important when discussing the physicochemical properties of steroidal drugs?

Molecular structure and environment Signup and view all the answers

What is a key characteristic that differentiates agonist and antagonist steroid activities?

Differences in molecular structure Signup and view all the answers

What is a prodrug?

A compound that requires metabolic conversion to become active Signup and view all the answers

What are the primary hormones secreted by females?

Estrogens and Progesterone Signup and view all the answers

What distinguishes steroid hormone action in target cells?

The presence of selective steroid hormone receptors Signup and view all the answers

In the two-step mechanism of steroid hormone action, what happens first?

Steroid hormones bind to nuclear membrane receptors Signup and view all the answers

What is the primary function of mineralocorticoids like Aldosterone?

Maintaining salt and water balance Signup and view all the answers

Which of the following is a glucocorticoid produced by the adrenal cortex?

Cortisol Signup and view all the answers

What regulates the secretion of Aldosterone?

The rennin-angiotensin system Signup and view all the answers

What is the main role of glucocorticoids like Cortisol?

Regulating carbohydrates and lipid metabolism Signup and view all the answers

How do steroid hormones achieve their physiological effects?

By activating specific genes in target cells Signup and view all the answers

What primarily regulates the secretion of Cortisol in the body?

Hypothalamus and pituitary gland Signup and view all the answers

What can happen when exogenous glucocorticoids are withdrawn?

Adrenal insufficiency may occur Signup and view all the answers

Which of the following is a therapeutic use of synthetic adrenal steroids?

Treating rheumatoid disease Signup and view all the answers

What is a common adverse effect of adrenal steroid usage?

Increased gluconeogenesis Signup and view all the answers

What structural feature increases the glucocorticoid activity of corticosteroids?

Insertion of α-CH3 groups at positions 6 and 16 Signup and view all the answers

What effect can corticosteroids have on body fat distribution?

Cause redistribution leading to a buffalo hump Signup and view all the answers

Which of the following statements about corticosteroids is true?

They can suppress inflammation regardless of the cause. Signup and view all the answers

How does the 9α-F group affect glucocorticoid activity?

Increases glucocorticoid potency Signup and view all the answers

What effect does the insertion of bulky substituents on the β-side of a molecule have on glucogenic activity?

It abolishes glucogenic activity. Signup and view all the answers

Which of the following steroids is the metabolite of Cortisone that is more active in vivo?

Cortisol Signup and view all the answers

Which enzyme is responsible for the reversible metabolism of hydrocortisone to cortisone in the liver?

11β-Hydroxysteroid dehydrogenase type-1 Signup and view all the answers

What is the primary role of 11β-HSD2 in the metabolism of steroids?

It inactivates hydrocortisone to cortisone. Signup and view all the answers

Insertion of which functional groups is known to abolish or reverse deoxycorticosterone activity?

16α-CH3 and 17α-CH3 Signup and view all the answers

What is the drug of choice for replacement therapy in patients with adrenocortical insufficiency?

Cortisone Signup and view all the answers

Which alteration to the steroid structure is known to enhance anti-inflammatory potency and glucocorticoid receptor affinity?

Conversion of 17α-hydroxyl to an ester or ether Signup and view all the answers

What is the effect of inserting a double bond between C1 and C2 on glucocorticoidal activity?

It increases glucocorticoidal activity. Signup and view all the answers

What is the primary role of 11β-HSD2 in the kidney?

To protect the mineralocorticoid receptor from glucocorticoids Signup and view all the answers

Which syndrome results from the deficiency of 11β-HSD2?

Apparent Mineralocorticoid Excess (AME syndrome) Signup and view all the answers

What modification is generally performed on synthetic corticosteroids?

Separate anti-inflammatory activity from mineralocorticoid effects Signup and view all the answers

What is the primary function of 11β-HSD1?

To convert cortisone to hydrocortisone Signup and view all the answers

Which corticosteroid derivative has about four times the anti-inflammatory activity of hydrocortisone?

Prednisone Signup and view all the answers

How does the geometry change in the ring-A of Δ1-corticoids affect their function?

It increases receptor affinity Signup and view all the answers

What is one of the main undesirable effects associated with most glucocorticoids?

Salt and water retention Signup and view all the answers

Which of the following effects of 11β-HSD1 is correlated with its presence in the liver?

Regulation of hepatic gluconeogenesis Signup and view all the answers

Study Notes

Steroids

Steroids are a class of chemical compounds vital in animal and plant biology. Examples include:
Sterols
Bile Acids
Steroidal Hormones
Steroids are widely used medicinally:
Birth Control
Hormone Replacement Therapy
Inflammatory Conditions
Cancer Treatment
Most steroids have a common structural backbone:
Steroid Backbone

Structure, Stereochemistry and Nomenclature of the Steroid Backbone

The steroid backbone consists of four fused rings:
Three Cyclohexane rings (A, B, C)
One Cyclopentane ring (D)
The numbering for steroid structures is unique.
Groups above the plane of the molecule are in the β-position, while those below are in the α-position.

Steroid Synthesis

All steroids are synthesized from cholesterol, which is synthesized from acetyl-CoA
Estrogen, Progesterone, and Testosterone exist in both males and females, but in different amounts:
Females primarily secrete Estrogens and Progesterone
Males primarily produce Testosterone
These differences in hormone production drive the development of distinct reproductive systems and physical characteristics between men and women.

Mechanism of Action

Steroid hormones act by regulating tissue-specific gene expression and protein biosynthesis in target cells.
They exhibit remarkable tissue specificity.
Steroid hormone receptors in different tissues are responsible for this specificity.
Steroid hormones act in a two-step process:
1. They bind to nuclear membrane receptors inside the cell to form an activated hormone-receptor complex.
2. The activated complex binds to DNA, triggering the expression of specific genes.

Adrenal Steroids

The adrenal gland produces two types of hormones:
Adrenal medulla: secretes catecholamines (primarily epinephrine)
Adrenal cortex: secretes adrenal steroids (corticosteroids)
Two main types of adrenal steroids are:
Mineralocorticoid (MC): - Primarily aldosterone - Regulates salt and water balance
Glucocorticoid (GC): - Primarily cortisol (hydrocortisone) - Regulates carbohydrate, lipid, and protein metabolism - Inhibits inflammation reactions - Suppresses immunity

Cortisol Production

The secretion of cortisol is controlled by the hypothalamus (through corticotropin) and the pituitary gland (through adrenocorticotropic hormone (ACTH)).
Cortisol and other glucocorticoids act as feedback inhibitors of both ACTH and corticotropin. This can lead to adrenal insufficiency when exogenous glucocorticoids are withdrawn.

Therapeutic Uses of Adrenal Steroids

Treat adrenal insufficiency (Addison’s Disease)
Manage rheumatoid diseases and allergic manifestations (e.g. severe asthma, rheumatoid arthritis, rheumatic fever)
Suppress inflammation regardless of the cause.
Important to note: Corticosteroids only provide palliative treatment and are not a cure.

Adverse Effects of Adrenal Steroids

Salt and water retention (hypertension and Cushing’s Syndrome)
Redistribution of body fat (Buffalo hump, Moon face)
Enhanced lipolysis and increased triglycerides
Inhibition of prostaglandins synthesis (can worsen peptic ulcers)
Increased gluconeogenesis (leads to glucose intolerance)

Structure Activity Relationships for Corticosteroids

Essential structural elements for activity:
C=O at C3
A double bond between C4 & C5
Oxygen at C11 (C=O or OH)
β-ketol side chain at C17
Factors that increase glucocorticoid activity:
α-CH3 groups at positions 6 and 16
9α-F group prevents metabolic oxidation and increases receptor dissociation
16α or β-CH3 blocks hydroxylation
All trans (B/C and C/D) backbone
11β-OH
Factors that decrease sodium retention:
16α-OH group
Bulky substituents on the β-side of the molecule abolish gluconeogenic activity, while those on the α-side do not.

Systemic Glucocorticoids

Cortisone:
11-keto analog of cortisol
Orally active
Used for replacement therapy in adrenocortical insufficiency
Cortisol (Hydrocortisone):
More potent and active
Primarily inactivated by 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1) in the liver.
Cortisone is inactivated by 11β-hydroxysteroid dehydrogenase type-2 (11β-HSD2) in the kidneys. This protects the mineralocorticoid receptor from glucocorticoids.

Synthetic Corticosteroids

Many synthetic derivatives have been developed with modified structures to:
Enhance anti-inflammatory activity while minimizing sodium and water retention.
Predinsone and Prednisolone:
Δ1-corticoids (dehydro derivatives of cortisone and hydrocortisone)
4 times the anti-inflammatory activity of their parent compounds.
The increased potency of these Δ1-corticoids results from a change in ring-A geometry which increases receptor affinity.

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Description

Explore the fascinating world of steroids, covering their chemical structure, biological roles, and medical applications. From understanding the steroid backbone to hormone synthesis, this quiz delves into essential concepts of steroid chemistry. Ideal for students in biology and chemistry courses.