Endocrine System and Cell Communication Notes

Cell Communication

  • Mechanisms of Intercellular Communication
    • Direct Communication
      • Transmission: Through gap junctions.
      • Chemical Mediators: Ions, small solutes, lipid-soluble materials.
      • Distribution of Effects: Usually limited to adjacent cells of the same type interconnected by connexons.
    • Paracrine Communication
      • Transmission: Through extracellular fluid.
      • Chemical Mediators: Paracrine factors (cytokines).
      • Distribution of Effects: Primarily limited to local area where concentrations are relatively high. Target cells must have appropriate receptors.
    • Endocrine Communication
      • Transmission: Through the circulatory system.
      • Chemical Mediators: Hormones.
      • Distribution of Effects: Target cells are primarily in other tissues and organs and must have appropriate receptors.
    • Synaptic Communication
      • Transmission: Across synaptic clefts.
      • Chemical Mediators: Neurotransmitters.
      • Distribution of Effects: Limited to very specific area. Target cells must have appropriate receptors.

Endocrine System Overview

  • Hypothalamus:
    • Production of ADH, oxytocin, and regulatory hormones.
  • Pituitary Gland:
    • Anterior lobe: ACTH, TSH, GH, PRL, FSH, LH, and MSH.
    • Posterior lobe: Release of oxytocin and ADH.
  • Thyroid Gland:
    • Thyroxine (T4)
    • Triiodothyronine (T3)
    • Calcitonin (CT)
  • Parathyroid Glands:
    • Parathyroid hormone (PTH)
  • Thymus:
    • Thymosins (Undergoes atrophy during adulthood)
  • Heart:
    • Natriuretic peptides: ANP and BNP
  • Adrenal Glands:
    • Adrenal medulla: Epinephrine (E), Norepinephrine (NE)
    • Adrenal cortex: Cortisol, corticosterone, aldosterone, androgens
  • Pineal Gland:
    • Melatonin
  • Kidney:
    • Renin
    • Erythropoietin (EPO)
    • Calcitriol
  • Adipose Tissue:
    • Leptin
    • Resistin
  • Digestive Tract:
    • Numerous hormones
  • Pancreatic Islets:
    • Insulin, glucagon
  • Gonads:
    • Testes (male): Androgens (especially testosterone), inhibin
    • Ovaries (female): Estrogens, progestins, inhibin

Chemical Messengers

  • Hormones, Autocrines, Paracrines
  • Autocrines and paracrines are local chemical messengers and are not considered part of the endocrine system.

Chemistry of Hormones

  • Two main classes:
    • Amino acid-based hormones:
      • Amines, thyroxine, peptides, and proteins
    • Steroids:
      • Synthesized from cholesterol
      • Estrogen, androgens, corticosteroids

Mechanisms of Hormone Action

  • Hormone action on target cells via receptors.
  • Receptors are:
    • On the cell membrane (Epinephrine, Norepinephrine, Dopamine)
    • Inside the cell (Steroids)
  • Water-soluble hormones
  • Lipid-soluble hormones (steroid and thyroid hormones).

Hormone Action via cAMP

  1. Hormone (1st messenger) binds receptor.
  2. Receptor activates G protein (Gs).
  3. G protein activates adenylate cyclase.
  4. Adenylate cyclase converts ATP to cAMP (2nd messenger).
  5. cAMP activates protein kinases.
  • Hormones that act via cAMP mechanisms: Epinephrine, ACTH, FSH, LH, Glucagon, PTH, TSH, Calcitonin.

Intracellular Receptors and Direct Gene Activation

  1. The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor.
  2. The receptor-hormone complex enters the nucleus.
  3. The receptor-hormone complex binds a hormone response element (a specific DNA sequence).
  4. Binding initiates transcription of the gene to mRNA.
  5. The mRNA directs protein synthesis.

Estrogen

  • Multiple pathways involving GPCRs, growth factors, and intracellular receptors influence gene expression and cellular growth.

EPO Function

  • EPO (Erythropoietin) promotes survival, differentiation, proliferation, and maturation of RBC progenitors and precursors through various signaling pathways (JAK2, PI3-Kinase, MAPK).

Stress and the Endocrine System

  • The hypothalamus releases CRH (corticotropin-releasing hormone) in response to stress, circadian rhythms, and inflammation (mediated by cytokines).
  • CRH stimulates the pituitary to release ACTH, which then stimulates the adrenal gland to produce cortisol.
  • Cortisol levels exhibit a circadian rhythm with a peak in the morning and a nadir at night.

Steroids and Drugs

  • Steroids like cortisol bind to glucocorticoid receptors, affecting gene transcription.
  • This can result in transactivation (synthesis of metabolic and endocrine peptides) or transrepression (less synthesis of proinflammatory cytokines) by influencing transcription factors like NFκB.

Target Cell Activation

  • Target cell activation depends on three factors:
    • Blood levels of the hormone.
    • Number of receptors on the target cell.
    • Binding affinity between the hormone and receptor.

Hormones in the Blood

  • Hormones circulate in the blood either free or bound.
  • Steroids and thyroid hormones are attached to plasma proteins.
  • All other hormones circulate without carriers.
  • The concentration of a circulating hormone reflects:
    • Rate of release.
    • Speed of inactivation and removal from the body.

Hormone Removal

  • Hormones are removed from the blood by:
    • Degrading enzymes.
    • Kidneys.
    • Liver.
  • Half-life: The time required for a hormone’s blood level to decrease by half.

Control of Hormone Release

  • Blood levels of hormones are controlled by negative feedback systems.
  • Hormone levels vary only within a range.
  • Hormones are synthesized and released in response to:
    • Humoral stimuli
    • Neural stimuli
    • Hormonal stimuli

Humoral Stimulus

  • Capillary blood contains a low concentration of Ca^{2+}, which stimulates the secretion of parathyroid hormone (PTH) by parathyroid glands.

Neural Stimulus

  • Preganglionic sympathetic fibers stimulate adrenal medulla cells to secrete catecholamines (epinephrine and norepinephrine).

Hormonal Stimulus

  • The hypothalamus secretes hormones that stimulate the anterior pituitary gland to secrete hormones that stimulate other endocrine glands.

Nervous System Modulation

  • The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms.
  • Example: Under severe stress, the hypothalamus and the sympathetic nervous system are activated, resulting in elevated body glucose levels.

Pituitary Gland and Hypothalamus

  • The pituitary gland (hypophysis) has two major lobes:
    • Posterior pituitary (lobe): Pituicytes (glial-like supporting cells) and nerve fibers.
    • Anterior pituitary (lobe) (adenohypophysis): Glandular tissue.

Posterior Pituitary

  1. Hypothalamic neurons synthesize oxytocin and ADH.
  2. Oxytocin and ADH are transported along the hypothalamic-hypophyseal tract to the posterior pituitary.
  3. Oxytocin and ADH are stored in axon terminals in the posterior pituitary.
  4. Oxytocin and ADH are released into the blood when hypothalamic neurons fire.

Pituitary-Hypothalamic Relationships

  • Anterior Lobe:
    • Originates as an out-pocketing of the oral mucosa.
    • Hypophyseal portal system:
      • Primary capillary plexus
      • Hypophyseal portal veins
      • Secondary capillary plexus
    • Carries releasing and inhibiting hormones to the anterior pituitary to regulate hormone secretion.

Anterior Pituitary

  1. Hypothalamic neurons secrete releasing and inhibiting hormones into the primary capillary plexus when appropriately stimulated.
  2. Hypothalamic hormones travel through the portal veins to the anterior pituitary where they stimulate or inhibit the release of hormones from the anterior pituitary.
  3. Anterior pituitary hormones are secreted into the secondary capillary plexus.
  4. Hormones include TSH, FSH, LH, ACTH, GH, PRL.

Anterior Pituitary Hormones

  • Growth hormone (GH)
  • Thyroid-stimulating hormone (TSH) or thyrotropin
  • Adrenocorticotropic hormone (ACTH)
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Prolactin (PRL)

Properties of Anterior Pituitary Hormones

  • All are proteins.
  • All except GH activate cyclic AMP second-messenger systems at their targets.
  • TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands).

Growth Hormone (GH)

  • Produced by somatotrophs.
  • Stimulates most cells, but targets bone and skeletal muscle.
  • Promotes protein synthesis and encourages the use of fats for fuel.
  • Most effects are mediated indirectly by insulin-like growth factors (IGFs).

Regulation of GH Release

  • GH release is regulated by:
    • Growth hormone-releasing hormone (GHRH)
    • Growth hormone-inhibiting hormone (GHIH) (somatostatin)

Actions of Growth Hormone

  • Direct action of GH:
    • Stimulates the liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors.
    • Mobilizes fats, elevates blood glucose by decreasing glucose uptake and encouraging glycogen breakdown (anti-insulin effect of GH).

Homeostatic Imbalances of Growth Hormone

  • Hypersecretion:
    • In children, it results in gigantism.
    • In adults, it results in acromegaly.
  • Hyposecretion:
    • In children, it results in pituitary dwarfism.

Growth Hormone Feedback

  • Hypothalamus secretes growth hormone-releasing hormone (GHRH) and somatostatin (GHIH).
  • GH increases, stimulates, reduces, and inhibits actions directly and indirectly through Insulin-like growth factors (IGFs) on skeletal, extraskeletal, fat, and carbohydrate metabolism.
    *

Thyroid-Stimulating Hormone (Thyrotropin)

  • Hypothalamus releases TRH which stimulates the anterior pituitary to release TSH, which then stimulates the thyroid gland to release thyroid hormones that target cells. Feedback inhibits TRH and TSH release.

Adrenocorticotropic Hormone (Corticotropin)

  • Secreted by corticotrophs of the anterior pituitary.
  • Stimulates the adrenal cortex to release corticosteroids.

Regulation of ACTH Release

  • Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm.
  • Internal and external factors such as fever, hypoglycemia, and stressors can alter the release of CRH.

Gonadotropins

  • Follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
  • Secreted by gonadotrophs of the anterior pituitary.
  • FSH stimulates gamete (egg or sperm) production.
  • LH promotes the production of gonadal hormones.
  • Absent from the blood in prepubertal boys and girls.

Regulation of Gonadotropin Release

  • Triggered by the gonadotropin-releasing hormone (GnRH) during and after puberty.
  • Suppressed by gonadal hormones (feedback).

Prolactin (PRL)

  • Secreted by lactotrophs of the anterior pituitary.
  • Stimulates milk production.

Regulation of PRL Release

  • Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine).
  • Blood levels rise toward the end of pregnancy.
  • Suckling stimulates PRH release and promotes continued milk production.