Endocrine Glands and Growth Hormone

Lecture 17: Endocrine Glands

Growth Hormone

• Growth depends on growth hormone.
• Other factors influence growth such as genetics, diet, chronic disease, stressful environment, and growth-influencing hormones.
• Factors responsible for growth are not the same throughout the growth period.
• In fetal growth, hormones from the placenta stimulate growth and GH plays no role.
• Postnatal growth spurt occurs during the first two years.
• Pubertal growth spurt occurs during adolescence.
• GH has metabolic functions unrelated to growth such as increasing protein and collagen synthesis and the transport of amino acids across cell membranes.
• GH increases fatty acid mobilization and use, such as increased lipolysis which is the breakdown of stored fat.
• GH decreases the rate of glucose/glycogen use.
• GH also has growth-promoting actions on soft tissues such as increasing cartilage growth and the number of cells (hyperplasia).
• GH increases the size of cells (hypertrophy).
• GH increases the number of cells by stimulating cell division and preventing apoptosis, which is programmed cell death.

Somatomedins

• They exert metabolic effects that are not related to growth are referred to as Insulin-like Growth Factors (IGF).
• Somatomedins increases fatty acid levels in blood by enhancing breakdown of triglyceride fat stored in adipose tissue
• Somatomedins Increase blood glucose levels by decreasing glucose uptake by muscles
• Two Somatomedins have been identified which include IGF-I (IGF-1) and IGF-II (IGF-2).
• IGF-I synthesis is stimulated by GH and mediates much of this hormone's growth-promoting actions.
• Blood plasma concentration of IGF-I normally mimics the rate of secretion of GH.
• The association with IGF-I allows the effects of GH to be more prolonged.
• IGF-II production is not influenced by GH.
• IGF-II is primarily important during fetal development.
• IGF-II continues to be produced during adulthood, but its role remains unclear.

Factors that Influence GH Secretion

• Factors influencing secretion of GH include Diurnal rhythm, Response to exercise, Stress and Low blood glucose.
• Growth hormone secretion is controlled by two antagonistic regulatory hormones known as Stimulatory (GHRH) and Inhibiting (GHIH).

Growth Hormone Imbalances

• Growth hormone deficiency stems from pituitary defect or hypothalamic dysfunction.
• Hyposecretion of GH can lead to dwarfism in children.
• Deficiency in adults produces relatively few symptoms.
• Growth hormone excess is caused by a tumor of GH-producing cells of the anterior pituitary.
• The symptoms depend on the age of individual when abnormal secretion begins.
• Gigantism is caused by overproduction of GH in childhood before epiphyseal plates close.
• Acromegaly occurs when GH hypersecretion occurs after adolescence.

Prolactin and Oxytocin

• In females, prolactin stimulates milk production by the breasts
• This is triggered by the hypothalamic prolactin-releasing hormone (PRH).
• Prolactin is inhibited by prolactin-inhibiting hormone (PIH)
• Blood levels of prolactin rise toward the end of pregnancy
• Suckling stimulates PRH release and encourages continued milk production

Oxytocin

• It plays a role in sexual arousal and orgasm in males and females and will help with uterine contractions.
• Oxytocin stimulates smooth muscle contraction in breasts and the uterus.
• In women producing milk, oxytocin triggers milk ejection referred to as the "letdown” reflex.
• In studies with non-human mammals, oxytocin promotes nest building, pup retrieval, acceptance of adopted offspring, and formation of adult pair-bonds.

Thyroid Gland

• Thyroid gland consists of two lobes of endocrine tissue joined in middle by narrow portion of gland.
• It is located over the trachea just below the larynx.
• It secretes of the thyroid hormones and calcitonin from two different cell types.
• Follicular cells are arranged into hollow spheres, which forms functional unit called follicle and is filled with colloid.
• Follicle lumen is an extracellular storage site for thyroid hormones.
• The follicular cells produces two iodine-containing hormones derived from tyrosine including Tetraiodothyronine (T4 or thyroxine) and Tri-iodothyronine (T3).
• There are also C cells in the thyroid gland that secrete a peptide hormone known as calcitonin
• T3 + T4 function in metabolism, mood, and body temperature.
• Calcitonin reduces calcium in the body and inhibits osteoclasts.

Synthesis, Storage and Secretion of Thyroid Hormone

• Basic ingredients include Tyrosine which is synthesized in sufficient amounts by body and Iodine which is obtained from dietary intake.
• The steps in synthesis occur on thyroglobulin molecules within colloid.
• In synthesis, tyrosine-containing thyroglobulin is exported from follicular cells into colloid by exocytosis.
• Thyroid captures iodine from blood and transfers it into colloid by iodine pump
• Within colloid, iodine attaches to tyrosine and a Coupling process occurs between iodinated tyrosine molecules to form thyroid hormones.
• Thyroid hormones remain in colloid during storage until they are split off and secreted.
• Generally, enough thyroid hormone is stored to supply body’s needs for several months.
• During Secretion follicular cells phagocytize thyroglobulin-laden colloid.
• Processed free T3 and T4 then diffuse across plasma membrane and into blood and most produced is T4 , which is then converted to T3.

Summary of Thyroglobulin-Laden Colloid

• Thyroid hormone secretion involves follicular cells "biting off" piece of colloid.
• The breaking of thyroglobulin molecule down to component parts and "spitting out" freed T3 + T4 into blood.
• Colloid is taken into follicular cells by phagocytosis, then lysosomes fuse with these vesicles and release digestive enzymes.
• The breakdown releases T3 and T4 as well as the inactive iodotyrosines.
• The thyroid hormones, being very lipophilic, pass freely through the outer membranes of the follicular cells and into the blood.
• It Quickly binds with several plasma proteins to be transported.
• The majority of circulating T4 and T3 is transported by thyroxine-binding globulin.
• Ninety percent of the secretory product released from the thyroid gland is in the form of T4.
• T3 is four times as potent in its biological activity.
• Most of T4 is converted into T3 by the liver and kidneys.

Thyroid Hormone Actions

• Thyroid hormone is main determinant of basal metabolic rate and heat production.
• It Influences synthesis and degradation of carbohydrates, fat, and protein.
• Increasing target-cell responsiveness to catecholamines creates a sympathomimetic effect
• Increasing heart rate and force of contraction creates a cardiovascular effect.
• It Plays crucial role in normal development of nervous system, creates a neural effect
• Also creates Skeletal muscle effect by increasing muscle size, calcium uptake, and shortening velocity of muscle

The Hypothalamus–Pituitary–Thyroid Axis

• It is Regulated by negative-feedback system that maintains relatively constant output.
• The following are included in the negative-feedback system: hypothalamic TRH, anterior pituitary TSH, and thyroid gland T3 and T4.

Hypothyroidism vs. Hyperthyroidism

• Hypothyroidism features include decreased BMR and cold intolerance, as well as decreased catecholamine sensitivity and muscle tone.
• Additional Hypothyroidism features also include constipation, hypoventilation, increased blood cholesterol and weight gain.
• Hyperthyroidism features include increased BMR and heat intolerance, as well as increased catecholamine sensitivity and muscle tone.
• Additional Hyperthyroidism features also include diarrhea, hyperventilation, decreased blood cholesterol and weight loss.

Calcitonin

• Calcitonin is a peptide hormone produced by the parafollicular, or C, cells that lowers blood calcium levels in children.
• It is an antagonist to parathyroid hormone (PTH).
• It targets the skeleton and inhibits osteoclast activity resulting bone resorption and inhibiting the release of calcium from the bone matrix
• It stimulates calcium uptake and incorporation into bone matrix.
• Its production levels are Regulated by a humoral (calcium ion concentration in the blood) negative feedback mechanism

Parathyroid Glands

• Parathyroid Glands: Tiny glands embedded in the posterior aspect of the thyroid.
• The cells are arranged in cords containing oxyphil and chief cells and the Chief (principal) cells secrete PTH, regulating calcium balance in the blood.

Effects of Parathyroid Hormone

• Rising Ca2+ in the blood inhibits PTH release whereas PTH release increases Ca2+ in the blood.
• PTH increases the absorption of Ca2+ by intestinal mucosal cells, enhances Ca2+ reabsorption by kidneys, and stimulates osteoclasts to digest bone matrix.

Adrenal Glands

• The gland is embedded above each kidney in a capsule of fat
• It consists of two endocrine organs of which the Outer portion is the cortex and Inner portion is the medulla.
• The adrenal cortex also consists of Zona glomerulosa (Mineralcorticoids), Zona fasciculata (Glucocorticoids), and Zona reticularis (Sex hormones).
• The adrenal medulla Consists of Catecholamines
• The adrenal glands are responsible for hormones, which include aldosterone, cortisol, androgens, Epinephrine, and Norepinephrine.

The Zona and Hormones

• Main mineralocorticoid produced is aldosterone, which helps to influence mineral balance, specifically Na+ and K+ balance
• The Principal action sites are on distal and collecting tubules of the kidney and will have a higher plasma concentration of K+.
• To increase secretion the hormone production requires activation of (Renin Angiotensin System) RAS.
• Factors related to a reduction in Na and BP as well as Direct stimulation of adrenal cortex by rise in plasma K+ Concentration are needed to increase hormone production
• Cortisol is the primary glucocorticoid
• Cortisol plays a key role in adaptation to stress.
• Cortisol shows Anti-inflammatory and immunosuppressive effects at pharmacological levels and Long-term use can result in unwanted side effects.
• This hormone also Displays a characteristic diurnal rhythm
• Cortisol also Peaks in the morning, and is lowest during evening in anticipation of wake time.
• The Hormone will help for metabolic fuels and building blocks available to help resist stress and increases blood glucose, amino acids, and fatty acids.
• The adrenal cortex secretes the same sex hormones as gonads, known as Androgens and Estrogen and progesterone.
• The level is mostly insignificant compared to total physiological pool but most only the adrenal sex hormone with biological importance is known as Dehydroepiandrosterone (DHEA).
• In males a # of androgens are converted but still overpowered by testicular testosterone.
• The sex Hormone is also converted in females for growth of pubic and axillary hair, Enhancement of pubertal growth spurt, Development and maintenance of female sex drive with hormone, contributing ~20% total testosterone production
• The Adrenal Medulla is the Modified part of sympathetic nervous system and will give a primary stimulus for increased adrenomedullary secretion.
• The hormone also helps to activate of sympathetic nervous system by stress, increasing synthesis of catecholamines.
• During Storage and release, Catecholamines are stored in chromaffin granules.
• With Secretion they are secreted into blood by exocytosis of chromaffin granules and generally released by adrenal medulla at same time.
• Epinephrine and norepinephrine: have varying affinities for two major classes of receptors: alpha-adrenergic and beta-adrenergic that help the body to stimulate a Sympathetic Effect.

Hormones Overview

• Secretion activated by stress will happen to increase a Dramatic increase in cortisol secretion in response to mentally and physically stressful situations.
• Hormone will help to increase in amount which makes a Large amounts of glucocorticoid will Inhibit every step of inflammatory response. Also very useful during effective drug for all alleric conditions such as rheumatoid and disorders and preventing organ transplant rejection.
• High Excessive hormones can Lead to having A side bad side with a high secretion of unwanted outcomes which will become: Loss of lean mass Increased risk of injury due to falls. Also can cause excessive eating habit, leading into high risks of diabetes with help from excess shunting of glucose.

Adipose Tissue, Anabolism, and Catabolism

• Anabolism: Buildup or synthesis of larger organic macromolecules from small organic subunits. Reactions usually require ATP. Reactions result in Manufacture of materials needed by the cell and Storage of excess ingested nutrients not immediately needed for energy production or use as cellular building blocks.
• Catabolism: Breakdown or degradation of large, energy-rich organic molecules within cells which will have two levels:
  1. Hydrolysis of large cellular molecules into smaller subunits
  2. Oxidation of smaller subunits to yield energy for ATP production.

Summary of the Major Pathways Involving Organic Nutrient Molecules.

• The summary starts with an Food intake which intakes in the form of Dietary protein, carbohydrate, and triglyceride fat. The process will then start Digestion in Absorbable units to produce Amino acids, Glucose, Fatty acids and Monoglycerides. Storage, structural, and functional macromolecules in cells are Body protein (structural or secretory products), Glycogen storage in Liver and Muscle, as well as Triglycerides in Adipose tissue stores. Use as metabolic fuel in cells are oxidation to where it will end with CO2 + H2O + ATP (for energy) , along with excess elimination from the system.

Circulation Overview and Use.

• Most interconversion occurs in the liver.
• Essential nutrients ( certain amino acids and vitamins)
• All food intake is has needed nutrients that is required to be stored for use between meals.
• Over Excess amounts of circulating glucose. Is known to be Stored in liver and muscle as Glycogen and Once liver and muscle stores are “filled up,” additional glucose is transformed into fatty acids and glycerol and stored in adipose tissue.

Role of Key Tissues in Metabolic States

• Liver has a Primary role in maintaining normal blood glucose levels and is a Principal site for metabolic interconversions such as gluconeogenesis
• The Adipose tissue helps for a Primary energy storage site
• Important in regulating fatty acid levels in the blood by storing and receiving fats throughout the body
• The Muscle the Primary site of amino acid storage while also as a Major energy user.
• The brains Normal operations are to only use glucose as an energy source while using a high amount, the has to stay constant at all times,
• The Pancreas produce to cells that creates 2 hormones are more Insulin and glucagon which important in regulating all fuel metabolism throughout all the other organs listed.

Insulin and Glucagon Hormones

• Endocrine cells ( pancreas) Islets of Langerhans which will help all the types.
  • [beta' cells are site of insulin synthesis and secretion.
  • alpha cells Produce glucagon
  • delta cells Pancreatic site of somatostatin synthesis
  • PP cells Secrete pancreatic polypeptide
• Insulin helps which will increase amino transportation and protein synthesis. It Is secreted into the state to have low rates, and can be lowed into low and the cell in order through through increase the rate through through all the state.
• Both hormone are important for the state adjustion and in general. Insulin and glucagon also have direct relationships. Insulin and Glucogen are more important in regulating fuel in general for the best out come.
  • Type 1 diabetes Insulin injection
  • Type 2 diet and exercise
• Is the only main problem or in state the increase of low blood sugar rate from.
• Insulin is most is know in helping low sugar is to get more
• Also help in rate of amino cells, the is for blood by a lot.

Reproductive Organs and Gonads

• Help is reproduction, and function in a lot during this system.
• All cell do reproduction parts, in most main of the main systems. All is needed for all the body parts, and organ to help the body.
• Hormone, does needed are the all the good stuff and system and other are not is needed.
• Is a state to get this hormone, it, not has test and not have has no more test and not for other and need to is high only and.
• Sperm are need for testosterone which, is a all all way are, test and in other system for test . Are a also needs for make of cells, sperm , and need for a lots of test .
• The hormone released what is low all a the cells.