Hormones and Homeostasis

Learning Objectives

• Understanding the broad role of the endocrine system
• Central Endocrine Glands lectured in first session
• Peripheral Endocrine Glands lectured in second session
• Compare mechanisms of intracellular communication
• Identify the functions of major hormones by organ system
• Explain how hormones coordinate physiological response to maintain homeostasis
• Explain how hormones coordinate to influence behavior

Central vs Peripheral Endocrine Glands

• Central includes the hypothalamus, anterior pituitary, posterior pituitary, and pineal gland
• Peripheral Endocrine Glands include the thyroid, adrenal gland, pancreas, and parathyroid

Thyroid Gland Anatomy

• Sits inferior to thyroid cartilage of the larynx
• Consists of two lobes connected by a narrow isthmus
• The main cells that secrete thyroid hormone, are organized into colloid-filled follicles
• Interspersed in the interstitial spaces between follicles are C cells, aka parafollicular cells
• C cells secrete calcitonin, lowering blood Calcium levels
• Thyroid hormone is synthesized and stored on thyroglobulin molecules

Thyroid Hormones

• Thyroid-stimulating hormone (TSH) from anterior pituitary influences thyroid gland
• T4 (thyroxine) and T3 (triiodothyronine) are released
• 93% of hormones relates are T4, less than 7% is T3
• T3 is more potent than T4
• T4 has a longer half life than T3
• T4 is converted to T3
• Thyroid hormones activate genes involved in glycolysis and ATP production

Thyroid Hormone Creation

• Iodine and Tyrosine are combined to create the components for T3 and T4
• Tyrosine and Iodine combine to make monoiodotyrosine
• Monoiodotyrosine and Iodine combine to make diiodotyrosine
• Monoiodotyrosine and Diiodotyrosine combine to make 3,5,3'-Triiodothyronine (T3)
• Diiodotyrosine and Diiodotyrosine combine to create 3,3',5'-Triiodothyronine (RT3)
• 3,3',5'-Triiodothyronine and Iodine combine to make Thyroxine (T4)

Synthesis, Storage, and Secretion Steps

• Thyroglobulin is synthesized
• Iodine moves from the blood to the colloid
• Iodine is oxidized by TPO (Thyroid Peroxidase)
• MIT + DIT combine to make T3, DIT + DIT combine to make T4
• Follicular engulf Tg-containing colloid.
• Iodide products split from Tg.
• MIT and DIT are deionized.
• TBG binds T3 and T4

Effects of Thyroid Hormone

• Thyroid hormones have slow onset and long duration of action
• Increase metabolism in almost all cells of the body
• Excessive quantities of the hormone can occasionally increase the basal metabolic rate by 60% to 100% above normal
• Production results in a calorigenic effect, responsible for increased energy consumption and heat generation in cells
• Results in strong, immediate, and short-lived increases in cellular metabilism

Physiological Functions of Thyroid Hormones

• Includes synthesis of new proteins, impacting many other systems
• Stimulates GH secretion and increase of IGF-I in the liver, influencing growth
• Sympathomimetic effect as well as heart rate, force of contraction and output, influencing the cardiovascular system
• Effects on the metabolism such as activating mitochondria, the Na+-K+-ATPase, O2 consumption, Glucose absorption, Gluconeogenesis, Glycogenolysis, Lipolysis, Protein synthesis, and BMR

Regulation of Thyroid Secretion

• Increased thyroid hormone decreases TSH via anterior pituitary
• Even when the anterior pituitary and when the anterior pituitary has been separated from the hypothalamus, this effect occurs

Thyroid Dysfunction

• Hypothyroidism is a secretion deficiency

• Hyperthyroidism is a secretion excess

• A goiter develops when the thyroid gland is overstimulated

• Hypothyroidism happens when there is primary failure of the thyroid gland, meaning that T3 and T4 hormone levels are low, however TSH is high

• Hypothyroidism happens when there is secondary failure of the thyroid gland from hypothalamus or anterior pituitary, meaning that T3 and T4 hormone levels are low, and so is TRH and/or TSH

• Hypothyroidism happens because of a lack of dietary iodine, in which T3 and T4 hormone levels are low, however TSH is high

• Hyperthyroidism happens because of presence of thyroid stimulating immunoglobulin (TSI) meaning T3 and T4, and TSH are all high and is stimulated by TSI

• Hyperthyroidism happens because of secondary excess caused by the hypothalamus or anterior pituitary, all hormones are therefore high

• Hyperthyroidism happens because of hypersecreting tumor, in which case TSH levels are low, while T3 and T4 hormone levels are high

Adrenal Glands Anatomy

• Each adrenal gland consists of the cortex and medulla
• The adrenal cortex consists of three distinct layers
• The adrenal medulla is functionally related to the sympathetic nervous system

Hormones

• From the adrenal cortex consist of mineralocorticoids (aldosterone), glucocorticoids (cortisol), and androgens (dehydroepiandrosterone)
• Aldosterone impacts sodium and potassium balance, as well as blood pressure homeostasis, from the zona glomerulosa
• Cortisol contributes to adaptation to stress, as well as metabolic regulation, and anti-inflammatory effects, produced by the zona fasciculata
• Androgens have an influence on early development of sex organs, produced by the zona reticularis
• The medulla consists of, releases adrenaline (epinephrine) and noradrenaline (norepinephrine), acting to reinforce the sympathetic nervous system, and increasing heart rate

Adrenal Medulla Makeup

• Consists of modified sympathetic postganglionic neurons
• Adrenaline and Noradrenaline have varying affinities for receptor types, specifically alpha and beta
• Adrenal medulla contains ~75% adrenaline (~75%) and noradrenaline (<25%)
• Neurons mostly noradrenaline, small amount of adrenaline with hormone is made in adrenal medulla

Cortisol Secretion Regulation

• Is regulated by hypothalamus, which influences pituitary, which influences the adrenal gland
• Adrenal cortex secretes males and female sex hormones
• The system has a diurnal rhythm and is linked to stress

Adrenal Gland Disorders

• Adrenal cortex may secrete too much or too little of any of its hormones
• Aldosterone hypersecretion can happen, (Conn's syndrome)
• Results in hypokalemia, increased blood volume, increased plasma sodium, and increased blood pressure
• Cortisol hypersecretion can happen (Cushing's syndrome / Cushing's disease).
• Adrenal androgen hypersecretion [eg. Polycystic ovary syndrome (PCOS)]
• Adrenocortical insufficiency can happen (Addison's disease)

Endocrine Pancreas & Fuel Metabolism

• The pancreas is composed of two major types of tissues: acini and & Islets of Langerhans
• Islets of Langerhans are most important in regulating fuel metabolism
• Is composed of of pancreatic hormones: insulin and glucagon
• Main cell types in islet of Langerhans, are ẞ cell which release insulin, and α cells that release glucagon, as ewll as D cells which release somatostatin

Insulin Details

• Human insulin is composed of two amino acid chains
• Connected to each other by disulfide linkages
• If split apart, function is lost
• Insulin secretion is increased by gastrointestinal effect, by the sympathetic nervous system and food intake.

Insulin Action

• Insulin enhances the concentration of glucose uptake and use inside muscle cells.
• Insulin must first bind with and activate insulin receptor protein to initiate its effects on target cells
• Blood glucose levels are influenced via sympathetic stimulation which stimulates glycogenolysis

Hyperglycemia and Diabetes Mellitus

• Means abnormally high glucose levels in the blood
• Diabetes mellitus is characterized By high glucose concentrations that overwhelmed reabsorption capabilities of kidneys
• Leads to glucose appearing presence in urine, polyuria along with urine volume becomes excessive
• Can be type I and II

Hypoglycemia & Glucagon

• Insulin at excess causes brain starving hypoglycemia
• Glucagon in general opposes the actions of insulin
• Glucagon secretion is increased during the postabsorptive state (fasting state)
• Insulin and glucagon work as a team to maintain blood glucose and fatty acid levels
• Elevated blood glucose stimulates insulin secretion, but inhibits glucagon secretion

The Roles of Somatostatin

• Somatostatin (aka GHIH) is made in the hypothalamus
• It inhibits the pituitary gland from secreting growth hormone (GH) and thyroid stimulating hormone (TSH)
• Somatostatin is also produced in the pancreas
• It Inhibits the secretion of insulin and glucagon and decreases utilization of the absorbed nutrients by the tissues

Bone Metabolism

• Bone remodeling is continuous for processes like mineralization and repair
• The intestinal absorption and fecal excretion relates to calcium and phosphate regulation.
• <1% of calcium is extracellular fluid.

• 98% of calcium is stored in bones.

• Bones store about 85% of phosphate.

Calcium Regulation

• Plasma Ca2+ tightly controlled to minimize changes in neuromuscular excitability and hormonal secretions
• Regulation controlled by balance of homeostasis/metabolism
• Parathyroid hormone (PTH) is crucial for life; raises free plasma Ca2+
• PTH action increases blood calcium and Calcitonin from (thyroid) decreases level

Bone Composition

• Bone continuously undergoes remodeling
• Bone is deposited via osteoblasts, and continuously resorbed in areas where osteoclasts are active
• Osteoblasts originate in bone marrow
• Osteoclasts from macrophages
• RANK Ligand (RANKL) and Osteoprotegerin (OPG) are important for bone generation

PTH Hormone Action

• Mechanical stress favors bone deposition

• PTH raises plasma Calcium

• PTH induces promoting localized dissolution of bone to put Ca2+ into plasma.

• Increased calcitonin means increased osteoblast activity, implying that blood calcium level lowers in concentration

• Incrased PTH = increase Osteoclast activity => increase of calcium in blood levels

PTH Impact On Kidneys

• PTH can act on the kidneys
• Phosphate metabolism depends on the same mechanisms as Ca² metabolism

Vitamin D and Calcium

• Vitamin D is activated to form dihydroxycholecalciferol
• Vitamin D is a steroid hormone, which increases calcium ion absorption in the intestine
• High Vitamin D stimulates the parathyroid by having a role in homeostasis

High PTH Main Effects

• Increased PTH in response to decreased extracellular fluid calcium results in:
• Urinary PO43, and PTH increases kidney Ca+ retention, so calcium leaves urine
• Causes a increase Intestinal vitamin D stimulated absorption

Explore the intricate roles of hormones in maintaining homeostasis, their mechanisms of action, and influence on behavior. Investigate endocrine gland regulation, hormone transport, and the interplay between hormone levels.