318 Lecture 11: Anterior Pituitary & Adrenal Cortex Cells

Cells of the Anterior Pituitary

• The chromophils are further subdivided into acidophils and basophils, according to their affinity for either acid or basic dyes.
• Acidophils are closely packed cells with pink spherical shapes.
• Basophils are closely packed cells with purple spherical shapes.
• Somatotropes produce Growth Hormone (GH).
• Lactotropes produce Prolactin (PRL).
• Thyrotropes produce Thyroid Stimulating Hormone (TSH).
• Corticotropes produce Adrenocorticotropic Hormone (ACTH).
• Gonadotropes produce Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH).

Layers of the Adrenal Cortex

• The adrenal cortex has three layers: zona glomerulosa, zona fasciculata, and zona reticularis.
• The zona glomerulosa is the thin, outer layer.
• The glomerulosa means "full of little balls".
• Cells in the zona glomerulosa are arranged in rounded clusters.
• The zona glomerulosa secretes mineralocorticoids, regulating electrolyte balance.
• The zona fasciculata is the thick, middle layer.
• Cells of the zona fasciculata are arranged in parallel cords separated by capillaries.
• The zona fasciculata makes up 3/4 of the adrenal cortex.
• Abundance of cytosolic lipid droplets in the zona fasciculata results in a foamy appearance.
• The cells are called spongiocytes in the zona fasciculata.
• The zona fasciculata secretes glucocorticoids which regulate fuel metabolism and androgens.
• The zona reticularis is the narrow, inner layer with cells in a branching network.
• The zona reticularis secretes glucocorticoids and androgens.

Glucocorticoids

• Glucocorticoids are corticosteroids produced in the adrenal cortex, specifically the zona fasciculata and zona reticularis.
• They affect the metabolism of carbs, protein, and fat.
• Glucocorticoids increase Hemoglobin(Hb) concentration.
• Glucocorticoids initiate the stress response and tissue repair.
• Glucocorticoids are anti-inflammatory.
• Examples of glucocorticoids are cortisol and corticosterone.
• Glucocorticoids lead to fat and protein catabolism, gluconeogenesis, and the release of fatty acids and glucose into the blood.

Neural Stimuli vs Hormonal Stimuli

• Short-term stress response includes increased heart rate and blood pressure.
• Short-term stress response includes the liver converting glycogen to glucose and releasing glucose to the blood.
• Short-term stress response includes dilation of bronchioles.
• Short-term stress response includes changes in blood flow patterns which leads to decreased digestive system activity and reduced urine output.
• Short-term stress response includes increased metabolic rate.
• Long-term stress response includes retention of sodium and water by kidneys, increased blood volume and blood pressure.
• Long-term stress response includes proteins and fats being converted to glucose or broken down for energy, increasing blood glucose and suppressing the immune system.

Glucocorticoids Effects

• Cortisol from the Pancreas counteracts insulin.
• Cortisol in bone reduces bone formation.
• Cortisol in the liver increases glucose generation.
• Cortisol in muscle decreases amino acid uptake by muscle.
• Cortisol in adipose tissue promotes the breakdown of fat.

Glucocorticoids Function

• Glucocorticoids promote gluconeogenesis and enzymes.
• Glucocorticoids regulate the mobilization of amino acids.
• Glucocorticoids promote glucose sparing.

Gluconeogenesis and the Cahill Cycle

• The glucose-alanine cycle, also known as the Cahill cycle or alanine cycle, involves muscle protein being degraded to provide more glucose to generate additional ATP for muscle contraction.
• Muscle and tissues that catabolize amino acids for fuel generate amino groups, mostly in the form of glutamate, through transamination.
• These amino groups are transferred via alanine aminotransferase to pyruvate to form alanine and alpha-ketoglutarate.
• Alanine moves through the circulatory system to the liver, converting back to pyruvate via alanine aminotransferase.
• Pyruvate is converted into glucose in the liver through gluconeogenesis, then transported back to muscle tissue.
• Glutamate is catabolized into ammonium by glutamate dehydrogenase in the mitochondria.
• Ammonium forms urea in the urea cycle.
• The Cahill cycle requires alanine aminotransferase (ALT), found in muscle, liver, and intestine.
• This pathway is used instead of the Cori cycle when an aminotransferase is present, there is a need to transfer ammonia to the liver, and the body is in a catabolic state.
• The gut dramatically increases glutamine consumption in catabolic states.
• The liver switches from glutamine producer to consumer for gluconeogenesis, relying on the skeletal muscle's ability/stores to maintain glutamine levels.
• This process is usually accompanied by a dramatic increase in muscle proteolysis, atrophy, and cachexia.

Glucocorticoids (GCs)

• Chronic excessive GC exposure impacts body composition and metabolism by causing whole-body insulin resistance and abdominal adiposity.
• Peripheral insulin resistance occurs due to impaired insulin signaling and glucose uptake.
• Excess GCs lead to muscle atrophy associated with elevated plasma fatty acids and triglycerides, altered hepatic carbohydrate and lipid metabolism, and impaired pancreatic β-cell function.
• GCs reduce bone density by increasing bone resorption while inhibiting bone formation, partly by decreasing osteoblast number and function.
• Chronic exposure to GC can cause excess abdominal and ectopic adipose tissue, dyslipidemia, cardiovascular disease, and decreased survival.

Mineralocorticoids

• Mineralocorticoids are corticosteroids that influence salt and water homeostasis and regulate electrolyte and fluid balance.
• Mineralocorticoids are produced in the adrenal cortex, specifically the zona glomerulosa.
• An example of a mineralocorticoid is aldosterone, which regulates blood pressure.
• Mineralocorticoids act through receptors in the distal convoluted tubule (DCT) and collecting tubules of the kidneys.
• Mineralocorticoids regulate sodium(Na+) and potassium(K+) levels.

Renin-Angiotensin System

• Kidneys detect low blood pressure & high Chloride (Cl-) levels and convert prorenin in blood to renin.
• Renin converts angiotensinogen from the liver to angiotensin I.
• Angiotensin I is converted to angiotensin II around pulmonary endothelial cells.
• Angiotensin II travels to the adrenal cortex, stimulating aldosterone production.
• Angiotensin II narrows blood vessels and stimulates aldosterone secretion.

Renin Release

• Renin secretion by granular cells occurs through three regulatory pathways: renal baroreceptors, macula densa, and the sympathetic nervous system.
• Renal baroreceptors respond to drops in renal perfusion pressure.
• Macula densa cells sense low Cl- in the DCT.
• The sympathetic nervous system and β adrenergic receptors directly stimulate renin release.

Estradiol

• Estradiol is an estrogen and a steroid.
• Estradiol is produced in the adrenal cortex and ovaries (follicles).
• It is produced in the Zona fasciculata & Zona reticularis.
• Estradiol maintains female reproductive tissues (e.g., oocytes, endometrium).
• Interstitial cells in testes can produce Estradiol
• Estradiol prevents sperm cell death.
• Estradiol supports skeletal & skin growth/maintenance.

Growth Hormone (GH)

• GHRH stimulates the anterior pituitary (AP) to release GH.
• The highest production of GH occurs in the AP.

• 1,000x more GH is produced than other AP hormones

• Has a short half-life (6-20 min).
• GH stimulates tissue growth, mitosis, and cell differentiation, especially in bone, cartilage, and muscle.
• GH decreases with age, resulting in less bone and muscle and more fat.
• The liver is a target of GH, and it secretes insulin-like growth factors I & II (IGFs).
• IGFs stimulate other target cells.
• IGF-II (Insulin-Like Growth Factor II) is found in fetal growth.

More on Growth Hormone (GH)

• GH is involved in protein synthesis, boosting transcription & translation.
• GH requires energy for fat metabolism.
• In adipocytes, GH releases fatty acids & glycerol, resulting in a protein-sparing effect.
• GH reduces carbohydrate metabolism, especially since the brain relies on glucose.
• GH stimulates gluconeogenesis in the liver.
• It causes electrolyte retention for building.

GH Effects

• GH decreases glucose uptake and increases lipolysis
• GH increases gluconeogenesis
• GH increases glycogenolysis
• Excessive GH induces hyperglycemia and insulin resistance.
• Under physiologic conditions, Insulin-like Growth Factor -1 (IGF-1) improves glucose homeostasis and enhances insulin sensitivity
• Indeed, administration of exogenous IGF-1 has been shown to promote glucose uptake in peripheral tissues.

GH and Cardiovascular System

• Effects of GH deficiency on atherosclerosis where decreased GH leads to decreased Insulin growth factor 1(IGF-1).
• Low Nitric oxide results from GH deficiency.
• Blue arrows indicate the effects produced by decreased GH secretion.
• Red arrows indicate how atherosclerosis is developed.
• Black arrows indicate increase or decrease.
• Green arrow indicate that the lack of GH leads to decreased IGF-I secretion

Interactions with other hormones

• IGF-1 inhibits GH secretion by:
  • Inhibiting GHRH release
  • Stimulating somatostatin release
• Ghrelin stimulates GH secretion
  • Secreted by stomach when empty
  • Interacts with hypothalamus, causing hunger
  • Also stimulates GHRH release. GH Release

Prolactin

• Prolactin-releasing hormone (PRH) from the Hypothalamus effects the Anterior pituitary gland, leading to prolactin production.
• Prolactin is a protein with a wide range of functions, including stimulating milk production (lactation) due to suckling and lower progesterone.
• It increases LH receptors in interstitial cells (males).
• Prolactin supports fetal development and neurogenesis.
• Prolactin supports immune tolerance and pulmonary surfactant synthesis.

Insulin

• Insulin is a peptide hormone produced by beta cells of pancreatic islets.
• It stimulates the uptake of glucose from the blood into the liver, fat, and skeletal muscles.
• Diabetes includes Type I and Type II.

Glucagon

• Glucagon is a peptide hormone produced by alpha cells of pancreatic islets.
• It is catabolic, increasing glucose and fatty acids in blood
• Glucagon is secreted if blood insulin (and glucose) is low.

Pancreas

• Insulin:
  • Stimulates glucose uptake by cells
  • Stimulates glycogen formation
• Glucagon:
  • Stimulates glycogen breakdown

Somatostatin

• Somatostatin is a peptide hormone produced by delta cells of pancreatic islets.
• It is a paracrine regulator of alpha and beta cells of the pancreas.
• Somatostatin production is stimulated by glucose and amino acids.
• It lowers stomach acid secretion and inhibits catecholamine secretion.
• Somatostatin receptors are associated with different roles of somatostatin in peripheral tissues.

Somatostatin ablation

• Somatostatin ablation leads to impaired pancreatic islet function and neonatal death in rodents.
• Somatostatin ablation leads to dysregulation of glucose homeostasis.
• Somatostatin ablation leads to excessive insulin and severe hypoglycemia.