9 - Steroid hormones 2-1

Hormone Classification

  • Hormones can be classified based on several criteria:

    • Chemical composition

    • Solubility properties

    • Receptor location

    • Nature of the signaling mechanism within cells

  • Group I: Lipophilic Hormones

    • Associate with plasma transport or carrier proteins post-secretion.

    • Process aids in solubility and prolongs half-life in plasma.

    • Binding dynamics are influenced by transport protein's quantity, affinity, and capacity.

    • Free hormone (biologically active form) crosses cell membranes easily and interacts with cytosolic or nuclear receptors.

    • The ligand-receptor complex acts as the intracellular messenger.

Water-Soluble Hormones

  • Group II: Water-Soluble Hormones

    • Bind to specific receptors on the plasma membrane of target cells.

    • Communicate intracellular processes via second messengers (e.g., cAMP, cGMP).

    • Epinephrine example: binds to receptors, increasing intracellular cAMP levels.

    • Atrial Natriuretic Factor (ANF): Uses cGMP as a second messenger.

    • Various hormones can utilize calcium (Ca2+) or phosphoinositides as intracellular signals.

    • Hormonal classification is flexible; new discoveries may alter categorizations.

Steroid Hormones

  • Derived from cholesterol, encompassing various classes:

    • Glucocorticoids (e.g., cortisol)

    • Mineralocorticoids (e.g., aldosterone)

    • Sex Hormones (e.g., androgens, estrogens, progestins)

  • Synthesized in:

    • Adrenal Cortex: cortisol, aldosterone, androgens

    • Ovaries/Placenta: estrogens, progestins

    • Testes: testosterone

Transport of Steroid Hormones

  • Transported via blood to target organs.

  • Due to hydrophobicity, they require binding with plasma proteins for transport.

    • Plasma albumin as a nonspecific carrier

    • Specific steroid-carrier proteins (e.g., corticosteroid-binding globulin for cortisol) provide more stable binding.

Synthesis of Steroid Hormones

  • Involves:

    • Shortening cholesterol’s hydrocarbon chain

    • Hydroxylation of the steroid nucleus

  • Rate-limiting reaction converts cholesterol to pregnenolone (21-carbon compound), the precursor for all steroids.

  • Pregnenolone is then modified to yield progesterone and further converted into other steroid hormones through hydroxylation.

Hormone Classes - General Features

Feature

Group I

Group II

Types

Steroids, Proteins

Glycoproteins

Solubility

Lipophilic

Hydrophilic

Transport proteins

Yes

No

Plasma half-life

Long (hours to days)

Short (minutes)

Receptor

Intracellular

Plasma membrane

Mediators

Receptor-hormone complex

cAMP, cGMP, etc.

Chemical Diversity of Hormones

  • Hormones synthesized from various building blocks, primarily cholesterol.

  • Steroid hormones like glucocorticoids, mineralocorticoids, and estrogens.

  • Progesterone: serves as a precursor for glucocorticoids, mineralocorticoids, testosterone, and estrogens.

  • Testosterone: becomes estradiol and dihydrotestosterone (DHT) in various tissues.

Polypeptides and Glycoproteins

  • Hormones vary in size and composition:

    • Small Hormones: Thyrotropin-releasing hormone (TRH) - 3 amino acids

    • Larger Hormones: ACTH (39 amino acids), PTH (84), GH (191)

Synthesis and Modification of Hormones

  • Hormones synthesized in various manners:

    • Immediate secretion (cholesterol-derived)

    • Storage for later release (e.g., catecholamines)

    • Processed from precursors when needed (e.g., insulin)

    • Conversion to active forms in the periphery (e.g., T3, DHT)

Hypothalamus and Hormonal Regulation

  • Neurosecretory cells in the hypothalamus produce:

    • Releasing hormones

    • Release-inhibiting hormones

  • ADH and oxytocin are secreted into the bloodstream from axon endings.

  • Anterior pituitary hormones are regulated by hypothalamic hormones.

Cholesterol-Derived Hormones

  • Synthesized from cholesterol in adrenal glands (cholesterol from plasma and synthesized from acetyl-CoA).

  • Upon ACTH stimulation, free cholesterol enters mitochondria for pregnenolone conversion by P450scc.

Aldosterone Production and Function

  • (Mineralocorticoid) produced in the zona glomerulosa of the adrenal cortex.

  • Acts mainly on kidneys to promote sodium and water reabsorption while excreting potassium.

  • Regulated by the RAAS (Renin-Angiotensin-Aldosterone System).

Cortisol Production

  • Regulated by ACTH from the anterior pituitary; involves several hydroxylation steps.

  • Functions:

    • Stress response regulation

    • Metabolism modulation

    • Inflammatory and immune responses management

Androgen Synthesis

  • Primarily dehydroepiandrosterone and androstenedione from adrenal cortex.

  • Convert to testosterone in peripheral tissues.

Testicular Steroidogenesis

  • Occurs in Leydig cells; similar mechanisms to adrenal steroidogenesis with LH promoting cholesterol conversion.

Testosterone Metabolism

  • Metabolized through oxidation or reduction to form DHT, the active form in many tissues.

  • Testosterone functions include:

    • Regulating sex differentiation and characteristics

    • Influencing spermatogenesis and fertility

    • Development of secondary male characteristics and anabolic effects.

Ovarian Steroidogenesis

  • Estrogens synthesized from androgens, with 17β-Estradiol as the main ovarian estrogen.

  • Unique features in ovarian synthesis compared to androgens.

Estrogen Biosynthesis

  • Involves aromatization of androgens with three hydroxylation steps.

  • Involves both theca and granulosa cells in synthesizing estradiol and estrone from androgens.