Endocrine System: Hormones and Regulation

• The endocrine system works with the nervous system to maintain homeostasis
• Endocrine glands, made of cells, tissues, and organs, secrete hormones into body fluids
• Organs of the endocrine system are not anatomically adjacent
• Hormones diffuse into the bloodstream and act on specific target cells some distance away
• Local hormones are messenger molecules that don't reach the bloodstream
• These messenger molecules include paracrine secretions (affect neighboring cells) and autocrine secretions (affect only the secretory cells)
• The body has two main types of glands: exocrine and endocrine
• Exocrine glands secrete products into ducts, outside the internal environment
• Endocrine glands secrete hormones into body fluids to affect target cells
• Major endocrine glands:
• Pituitary, thyroid, parathyroid and adrenal glands
• Pancreas, pineal, thymus, reproductive glands (ovaries and testes), and kidneys
• Specialized cells in various organs produce hormones but are part of other systems like the liver, heart, and gastrointestinal tract
• Both the nervous and endocrine systems communicate with cells, but have differences
• The nervous and endocrine systems are precise in their action on specific target cells
• The endocrine system communicates with target cells using chemical messengers called hormones
• The nervous system uses neurotransmitters
• Endocrine glands and their hormones regulate metabolic processes within cells and the whole body

Other Chemical Messengers

Paracrine secretions (local hormones)

• Substances secreted into the interstitial fluid by certain glands
• Substances breakdown rapidly so they do not reach the bloodstream
• Act only on nearby cells but in a manner similar to hormones
• Example: Histamine released from white blood cells dilates local blood vessels

Autocrine secretions

• Act only on the cells that secrete them
• Example: Substance secreted by liver cells causes them to release iron

A Comparison Between Nervous & Endocrine Systems

Hormone Action

• Structurally, the two types of hormones are steroids and nonsteroids
• Steroids are steroid-like substances derived from cholesterol
• Nonsteroids are amines, peptides, proteins, or glycoproteins, produced from amino acids
• Types of Hormones

Steroid Hormones

• Steroid hormones are lipid-soluble so they can pass through cell membranes
• Steroid hormones are carried in the bloodstream weakly bound to plasma proteins
• This bloodstream binding prevents rapid degradation
• Protein receptors for steroid hormones are located inside the target cell
• The hormone-receptor complex binds with the DNA and activates specific genes
• This activation directs the synthesis of specific proteins like enzymes, transport proteins, or hormone receptors that carry out steroid hormone effects

Nonsteroid Hormones

• Nonsteroid hormones are soluble in water and cannot penetrate the phospholipid bilayer of cell membranes
• Nonsteroid hormones combine with receptors in target cell membranes with a binding site and activity site
• The hormone is called the first messenger
• Chemicals respond to binding of the hormone and cause changes in the cell called second messengers
• Cascade of biological activity through cell membrane, beginning with hormone binding - signal transduction
• The hormone-receptor complex generally activates a G protein
• This protein activates the enzyme adenylate cyclase on the inside of the cell membrane
• Adenylate cyclase breaks down ATP to cAMP, which activates protein kinases
• Protein kinases phosphorylate other proteins, activating them, and carrying out hormone effects

Prostaglandins

• Lipids produced from the fatty acid, arachidonic acid, in cell membranes
• Prostaglandins are produced by cells in many organs
• Prostaglandins are potent in small amounts
• Prostaglandins act locally affecting the organ in which they are produced
• They are produced when needed, and inactivated after effects are exerted rather than stored
• Prostaglandins produce regulatory effects, like relaxing/contracting smooth muscle
• Stimulate secretion of other hormones/chemicals and influence blood pressure/reproductive physiology

Control of Hormonal Secretions

• Hormone levels are precisely regulated
• Release of hormones from the hypothalamus controls secretions of the anterior pituitary
• Anterior pituitary hormones affect the activity of peripheral endocrine glands
• The nervous system influences certain endocrine glands directly via nerve impulses
• Other glands respond directly to changes in the internal fluid composition, such as the level of glucose or a particular ion
• Hormone release is generally controlled by negative feedback mechanisms
• In this system a gland is sensitive to the concentration of the substance it regulates
• As hormone level rises, it exerts effects and further secretion is inhibited
• When the concentration drops below its normal level, the gland begins secreting again
• This is how hormone levels remain fairly constant within a normal average range

Pituitary Gland

• Pituitary gland (hypophysis) is attached to the hypothalamus by a stalk called the infundibulum

Anterior pituitary (anterior lobe)

• Consists mostly of glandular epithelial tissue
• Arranged around blood vessels and enclosed in collagenous connective tissue

Posterior pituitary (posterior lobe)

• Part of the nervous system
• Consists of axons of hypothalamic neurons

Control of the Pituitary Gland by the Hypothalamus

Anterior pituitary

• Releasing and inhibiting hormones from the hypothalamus control secretion from the anterior pituitary
• These hormones are carried in bloodstream in the pituitary stalk to the anterior pituitary
• Anterior pituitary cells are stimulated to release or stop releasing hormones

Posterior pituitary

• The posterior pituitary stores hypothalamic hormones
• It then releases them into the blood in response to nerve impulses from the hypothalamus

Anterior Pituitary Hormones

Growth Hormone (GH)

• Stimulates body cells to grow and reproduce
• Speeds the rate at which cells use carbohydrates and fats
• Growth hormone-releasing hormone (GHRH) from the hypothalamus increases the amount of GH secreted
• GH inhibiting hormone (GHIH, somatostatin) inhibits it
• Nutritional status also affects the release of GH; more is released when glucose is low, or when certain amino acids increase
• GH imbalances:
  • Pituitary dwarfism - due to childhood GH deficiency
  • Gigantism - due to childhood GH oversecretion
  • Acromegaly - due to adulthood GH oversecretion

Prolactin (PRL)

• Promotes milk production after birth
• Prolactin releasing factor (PRF) and prolactin inhibiting hormone (PIH) from the hypothalamus controls milk production
• There is no known normal physiological role in males

Thyroid-stimulating hormone (Thyrotropin or TSH)

• Controls secretion of hormones from the thyroid gland
• Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates TSH release
• As the blood concertation of thyroid hormones increase, secretions of TRH and TSH will decrease

Adrenocorticotropic hormone (ACTH)

Controls the adrenal cortex secretion of certain hormones

• Corticotropin-releasing hormone (CRH) from the hypothalamus regulates the release of the adrenocorticotropic hormone
• Stress can also increase release of CRH, to increase ACTH secretion

Gonadotropins (FSH and LH)

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) affect the gonads (testes in the male and ovaries in the female)

• In males, LH is also known as interstitial-cell stimulating hormone (ICSH)

Posterior Pituitary Hormones

• Hypothalamic neurons produce antidiuretic hormone (ADH) and oxytocin (OT)
• These hormones are then stored in the posterior pituitary
• Impulses from the hypothalamus then releases the hormones from posterior pituitary These travel down hypothalamic axons to the storage area in the posterior pituitary
• Although these two hormones are synthesized in the hypothalamus, they are called posterior pituitary hormones because they are released there

Antidiuretic hormone (ADH or vasopressin)

• Causes the kidneys to conserve water reducing the amount of water excreted in the urine
• The hypothalamus regulates the secretion of ADH, based on the amount of water in body fluids
• Osmoreceptors detect changes in osmotic pressure in body fluids, and adjust ADH secretion
• At high level, also causes vasoconstriction of blood vessels, which helps to maintain blood pressure in dehydration
• Diabetes insipidus is a condition resulting from insufficient ADH

Oxytocin (OT)

Plays a role in childbirth by contracting uterine wall muscles

• It plays a role in milk ejection by forcing milk into ducts from the milk glands during breastfeeding
• Stretching of the uterine and vaginal tissues in the latter stages of pregnancy stimulates release of oxytocin Suckling of an infant at the breast stimulates release of oxytocin when it is released after childbirth
• This release is controlled through positive feedback

Hormones of the Pituitary Gland

Thyroid Gland

• Located below the larynx
• Consists of two broad lobes connected by an isthmus
• Two thyroid gland hormones help control caloric intake
• One helps regulate blood calcium level and bone growth

Structure

• The thyroid is made up of secretory units called follicles
• These follicles are filled with stored hormones/colloid
• Follicular cells secrete hormones that can be stored in the colloid, then released into the blood

Hormones

Follicular cells

• Produce two iodine-containing hormones: thyroxine (T4 or tetraiodothyronine), and triiodothyronine (T3)
• T3 is the more potent hormone
• These two hormones have similar actions
  • They regulate the metabolism of carbohydrates, lipids and proteins
  • They also increase the rate at which cells release energy from carbohydrates
• Enhance protein synthesis, and stimulate the breakdown and mobilization of lipids
• Thyroid hormone level is the major factor in determining basal metabolic rate (BMR) -BMR is the caloric intake necessary to maintain life
• These hormones are essential for normal growth, development, and nervous system maturation
• Hypothalamus and pituitary gland control the release of thyroid hormones
• Iodine is needed by the follicular cells to make them

Extrafollicular (parafollicular) cells

• Secrete calcitonin, a hormone which lowers blood calcium and phosphate ions when high
• Calcitonin increases calcium deposition in bones by inhibiting osteoclast activity
• It increases calcium and phosphate excretion by the kidneys into urine
• Release of calcitonin is regulated by the blood concentration of calcium

Thyroid Disorders

Hypothyroidism

• Underactivity of the thyroid gland
• low metabolic rate, fatigue and weight gain in adults
• Cretinism in infants causes poor growth and bone formation, abnormal mental development, sluggishness

Hyperthyroidism

• Overactivity of the thyroid gland
• Causes high metabolic rate, restlessness, overeating in adults
• May lead to eye protrusion (exophthalmia)
• Either hypo- or hyperthyroidism may cause a goiter, an enlarged thyroid that appears as a bulge in the neck

Hormones of the Thyroid Gland

Parathyroid Glands

• Four tiny parathyroid glands located on posterior side of thyroid gland
• The glands consist of tightly packed secretory cells covered by a thin capsule of connective tissue
• Secretory cells are associated with capillaries

Parathyroid Hormone (PTH)

Increases blood calcium ion concentration and decrease phosphate ion concentrations. • PTH stimulates bone resorption by osteoclasts, which releases calcium into the blood. • PTH also stimulates the kidneys to conserve calcium. • PTH activation of vitamin D by the kidney, increasing absorption of calcium in the intestines • Blood calcium levels regulate hormone release via negative feedback loop

Calcium Regulation

• Hormones from the thyroid and parathyroid glands, as well as vitamin D, function to regulate calcium levels
• Calcitonin and PTH maintain proper blood calcium concentration
• Calcitonin and PTH exert opposite effects in blood calcium levels

Calcium in blood:

PTH increases blood calcium when it is too low.

• Calcitonin decreases blood calcium when it is too high, by increasing deposition in bones
• Parathyroid hormone disorders

Hypoparathyroidism

• PTH deficiency due to surgical removal or injury reduces blood calcium

Hyperparathyroidism

• PTH excess due to parathyroid tumor, increasing blood calcium

Adrenal Glands

• The adrenal glands sit on top of the kidneys enclosed in layers of adipose and connective tissue

Structure

The pyramid-shaped glands consist of inner adrenal medulla and outer adrenal cortex

• Adrenal medulla - modified postganglionic neurons connected to the sympathetic nervous system
• Adrenal cortex - epithelial cells in three layers:
  • Outer zona glomerulosa
  • Middle zona fasciculata
  • Inner zona reticularis

Hormones of the Adrenal Medulla

Secretes epinephrine and norepinephrine into the bloodstream

• These two hormones are similar in structure and function
• Adrenal medulla secretes 80% epinephrine and 20% norepinephrine
• Effects resemble those of sympathetic neurotransmitters of the same name, except that adrenal hormones last up to 10 times longer
• These hormones are used in stress and “fight or flight” responses
• Their effects include:
  • increase heart rate
• elevate blood pressure
• increment of blood glucose
• expanding airways
• decrease of digestive activities
• Release of medullary hormones is regulated by nerve impulses from the central nervous system through the sympathetic division of the autonomic nervous system

Hormones of the Adrenal Cortex

• Adrenal cortex cells produce over 30 steroids, some of which are hormones that are vital to survival
• Most important hormones are aldosterone, cortisol, and the sex hormones.
• Aldosterone (mineralocorticoid)
  • Secreted by cells of the outer layer of the cortex
  • Helps regulate mineral/electrolyte balance
  • Causes the kidneys to conserve sodium ions (and thus water), and to excrete potassium ions in the urine
  • Secreted in response to decreasing blood volume and blood pressure; these changes are detected by the kidney
• Cortisol
  • It’s a glucocorticoid
  • regulates glucose metabolism
• Produced by cells of the middle layer of the adrenal cortex
• Its functions include Inhibits protein synthesis, increasing blood amino acids Promotes fatty acid release from adipose tissue, increasing use for energy and decreasing the usage of glucose.
• It causes liver cells to produce glucose from noncarbohydrates, increasing blood glucose A negative feedback mechanism involving CRH from the hypothalamus and ACTH from the anterior pituitary regulates cortisol release. Stress, injury, or disease also triggers this release Adrenal Sex hormones
• Produced in innermost layer of cortex (the Zona Reticularis)
• Mostly male hormones (adrenal androgens), but can be converted to female hormones in skin, liver and adipose tissue Supplement those released by gonads and may stimulate early development of reproductive organs Disorders
• Addison disease: hyposecretion of glucocorticoids and mineralocorticoids.
• Cushing syndrome: hypersecretion of adrenal cortical hormones.

Comparative Effects of Epinephrine and Norepinephrine

Hormones of the Adrenal Cortex

Pancreas

• The pancreas is an endocrine and exocrine gland
• It secretes hormones as an endocrine gland and secretes digestive juice into the digestive tract as an exocrine gland
• Pancreatic hormones control blood glucose level

Structure

• Elongated organ posterior to the stomach
• Endocrine portions called pancreatic islets/islets of Langerhans
• These contain alpha cells (secrete glucagon)
• Beta cells (secrete insulin)
• Pancreatic duct joins the pancreas to the duodenum, for digestive juice to enter duodenum of small intestine

Pancreatic Secretions

Secretes the hormones glucagon (alpha cells) and insulin (beta cells) to control blood glucose Glucagon secretion

• Increases the blood level of glucose, by stimulating the breakdown of glycogen and the conversion of noncarbohydrates into glucose by the liver
• The release of glucagon is controlled by negative feedback
• Low blood glucose stimulates this secretion

Insulin secretion

• Decreases the blood level of glucose by stimulating the liver to form glycogen
• It promotes facilitated diffusion of glucose into cells, increases protein synthesis, and stimulates adipose cells to store fat
• The release of insulin is controlled by negative feedback
• High blood glucose stimulates it
• Insulin and glucagon coordinate to maintain a relatively stable blood glucose concentration

Diabetes Mellitus

• Metabolic disease from lack of insulin or inability of cells to recognize insulin
• High blood glucose harms the eyes, heart, blood, peripheral nerves Causes disturbances in carbohydrate, fat and protein metabolism
• Glucose entry into body cells are impaired
• Symptoms: hyperglycemia, glycosuria, polydipsia, polyphagia, and acidosis
• Type 1 diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) is an autoimmune disorder, characterized by beta cell destruction
• Characterized by decreased or stopped insulin production
• Type 2 diabetes mellitus (noninsulin-dependent diabetes mellitus, NIDDM) - insulin is produced but not recognized by cells

Pineal, Thymus, and Other Endocrine Tissues and Organs

Pineal Gland

• Located near the upper portion of the thalamus
• It secretes melatonin, which regulates circadian rhythms
• Melatonin is released at night and suppressed during the day
• It supports the proper regulation of the sleep cycle and hormone levels

Thymus Gland

• Lies between the lungs, behind the sternum
• Secretes thymosins, which affect the production and differentiation of T lymphocytes, which are important in immunity
• Largest in children shrinking as they age due to decreasing T lymphocyte production

Other Endocrine Tissues and Organs

Reproductive Organs- The ovaries produce estrogen and progesterone

• The placenta produces estrogen, progesterone, and gonadotropin
• The testes produce testosterone Digestive Organs- The digestive glands secrete hormones associated with the stomach and small intestine Fat-Cells of Adipose Tissue
• Secrete leptin, a hormone that helps regulate food intake and energy balance
• When fat stores increase, leptin level increases and appetite is suppressed Heart
• Secretes atrial natriuretic peptide, which affects sodium and water excretion by the kidneys. Kidneys
• They secrete erythropoietin (EPO) for blood cell production

Stress and Health

• Factors (stressors) that threaten homeostasis
• Stressors increase sympathetic nervous system activity

Stress:

May be physical, psychological, or both.

• Physical stress threatens survival of tissues
• Extreme cold, prolonged exercise, oxygen deficiency, or infections
• Psychological stress results from real or perceived dangers, anger, depression, fear, and grief
• Even pleasant stimuli sometimes cause stress

Responses to Stress

Responses maintain homeostasis

• These responses involve a set of reactions called general adaptation syndrome (GAS) The stress response has two stages: alarm and resistance

Alarm/Immediate "fight or flight"

-Blood glucose and fatty acids increase -Heart rate, breathing rate, and blood pressure rise -Adrenal medulla increases epinephrine(Adrenaline) and Norepinephrine release -Air passages dilate

• Blood to skeletal muscles increases while it decreases in the Skin and digestive organs

Longer-lasting resistance stage

• CRH from the hypothalamus travels to the anterior pituitary stimulating ACTH secretion
• Cortisol is then secreted from the adrenal cortex, which causes
• Elevated blood amino acids
• Elevated fatty acid release
• Elevated glucose formation from noncarbohydrates
• This leads to long-term stress causing: -Decreases in Lymphocytes, which lowers our resistance to infections and some cancers
• Increased risk of high blood pressure, atherosclerosis, and Gl ulcers