11- BCC Steroids Handout

Learning Objectives

  • At the end of this lecture, students should be able to:

    • Describe the major roles steroids play in metabolism.

    • Know the major steroid hormone classes.

    • Understand the hormonal stimulation as well as steps of steroid biosynthesis.

    • Describe steroid hormone synthesis in major sites in the body.

    • Describe the mechanism of action of steroid hormones.

    • Describe how glucocorticoids and mineralocorticoids work in the body.

    • Give examples of how corticosteroids are used in medicine.

Overview of Steroid Hormones

  • Physiological Regulation: Steroid hormones regulate numerous bodily processes, including:

    • Development and function of the reproductive system.

    • Carbohydrate metabolism.

    • Mineral balance.

    • Inflammatory responses.

    • Stress responses.

    • Bone metabolism.

    • Cardiovascular fitness.

    • Behavior and mood.

    • Cognition.

Steroid Hormone Synthesis

  • Synthesis Details:

    • Steroid hormones are synthesized and released immediately.

    • All are derived from cholesterol.

    • Progestins are precursors to all other steroid hormones.

    • Enzymes responsible for production are located in mitochondria and smooth endoplasmic reticulum (ER).

    • Due to being lipid soluble, steroids are permeable to membranes and thus not stored in cells.

Major Classes of Steroid Hormones

  1. Cholesterol

  2. Progestins

  3. Glucocorticoids

  4. Androgens

  5. Mineralocorticoids

  6. Estrogens

Key Steroid Hormones and Functions

  • Pregnenolone (C-21): Precursor for all C18, C19, and C21 steroids, produced from cholesterol by desmolase.

  • Progesterone (C-21): Maintains uterine endometrium; differentiation factor for mammalian glands.

  • Estradiol (C-18): Regulates gonadotrope secretion in ovarian cycle; negative feedback on testosterone synthesis.

  • Testosterone (C-19): Produced from progesterone; promotes sperm protein production in Sertoli cells.

  • Aldosterone (C-21): Regulates blood pressure and fluid volume; stress-related increases.

  • Cortisol (C-21): Dominant glucocorticoid; numerous effects on immune system and stress adaptation.

  • 1,25-Dihydroxyvitamin D3 (Calcitriol): Regulates calcium and phosphorus homeostasis.

Hormonal Stimulation of Steroid Biosynthesis

  • Dependent on Cell Type and Receptor:

    • ACTH for cortisol, FSH for estradiol, LH for testosterone.

  • Process begins when hormones bind to cell membrane receptors activating adenylate cyclase and increasing intracellular signaling cascades leading to increased steroid hormone synthesis.

  • Desmolase is crucial for initiating the synthesis of progestins from cholesterol.

Key Enzymes in Steroid Biosynthesis

  • Desmolase (P450scc, CYP11A): Converts cholesterol to pregnenolone, a rate-limiting step.

  • Other CYP proteins modify pregnenolone into various steroid hormones through multiple hydroxylation reactions.

Congenital Adrenal Hyperplasias (CAH)

  • Types of Deficiencies:

    • 3B-Hydroxysteroid Dehydrogenase Deficiency: No glucocorticoids, mineralocorticoids, and sex hormones produced; female-like genitalia in affected females, autosomal recessive.

    • 17α-Hydroxylase Deficiency: Leads to hypertension due to mineralocorticoid overproduction; absence of sex hormones.

    • 21α-Hydroxylase Deficiency: Most common, leads to salt-wasting or virilization due to androgen overproduction.

    • 11β-Hydroxylase Deficiency: Causes hypertension from deoxycorticosterone overproduction.

Steroid Production Sites

  • Adrenal Cortex:

    • Zona Glomerulosa: Aldosterone (mineralocorticoid).

    • Zona Fasciculata: Cortisol (glucocorticoid).

    • Zona Reticularis: Androgens.

  • Testes: Produce testosterone and dihydrotestosterone.

  • Ovary: Produce progesterone and estradiol.

Mechanism of Action of Steroid Hormones

  • Steroid hormones are lipophilic and bound to protein carriers (e.g., ABP, SHBG) in the blood, allowing them to avoid metabolism and assist in maintaining hormone levels.

  • They bind to intracellular receptors and initiate gene transcription, leading to long-lasting effects due to protein synthesis.

  • Commonly induces complex hormonal regulation, including effects on glucose metabolism and actions in various tissues.

Side Effects of Glucocorticoids and Mineralocorticoids

  • Glucocorticoids: Can lead to muscle atrophy, obesity, metabolic syndrome, osteoporosis, impaired insulin action, and negative feedback on adrenal hormones.

  • Mineralocorticoids: Aldosterone plays a crucial role in electrolyte and fluid balance; disorders can lead to life-threatening imbalances.

Clinical Relevance of Steroid Hormones

  • Cushing's Syndrome: Excess glucocorticoids present with personality changes, hypertension, and characteristic physical features (moon face, thin skin).

  • Therapeutic Uses: Importance in managing inflammatory conditions, hormone replacement therapies, and as immunosuppressants in various diseases.