The Endocrine System

The Endocrine System

• Releases hormones into the bloodstream.
• The nervous and endocrine systems release chemical messengers that bind to target cells.
• These systems coordinate body functions and maintain homeostasis.

Similarities Between Nervous and Endocrine Systems

• Both rely on chemicals binding to specific receptors on target cells.
• They share chemical messengers; neurotransmitters in the nervous system and hormones in the endocrine system.
• Both are primarily regulated by negative feedback mechanisms.
• The common goal is to preserve homeostasis by coordinating and regulating cells, tissues, organs, and systems.

Differences Between Nervous and Endocrine Systems

• The nervous system uses electrical impulses (APs) and neurotransmitters for fast responses and brief effects, acting on specific targets.
• The endocrine system uses hormones for slow responses and longer-lasting effects, acting on many targets with powerful effects even in low concentrations.

Functions of Hormones

• Hormones help regulate chemical composition and volume of internal environment, metabolism, muscle contraction, glandular secretions, and immune system activities.
• Hormones also control growth and development, regulate reproductive systems, and establish circadian rhythms.

Hormone Origin

• Exocrine glands secrete products into ducts, while endocrine glands secrete into interstitial fluid, diffusing into the blood.
• Endocrine glands include the hypothalamus, pituitary, thyroid, parathyroid, adrenal, pineal, and pancreatic islets.
• Secondary hormone-producing organs include the heart, thymus, digestive tract, kidneys, and gonads.

Hormone Activity

• Hormones influence target cells by binding to specific protein receptors.
• Only target cells have receptors for a given hormone.
• Receptors are constantly synthesized and broken down, leading to down-regulation and up-regulation.
• Hormones can act systemically (circulating) or locally.

Down-Regulation

• Excess hormone levels decrease the number of receptors in/on the cell, reducing sensitivity.

Up-Regulation

• Hormone deficiency increases the number of receptors to increase sensitivity.

Circulating Hormones

• Circulate in the blood throughout the body and last longer.

Local Hormones

• Act locally and are inactivated quickly, not circulating in the blood.
• Paracrine act on neighboring cells
• Autocrine act on the same cell that secreted them

Chemical Classes of Hormones

• Two main classes are lipid-soluble and water-soluble hormones.

Lipid-Soluble Hormones

• They bind to transport proteins, temporarily making them water-soluble.
• They slow passage through kidney filtration.
• They provide a hormone reserve in the bloodstream.
• Steroid hormones are derived from cholesterol (e.g., testosterone & estrogen).
• Thyroid hormones' tyrosine rings make T3 and T4 very lipid-soluble.
• Nitric Oxide (NO) acts as both a neurotransmitter and a hormone.

Water-Soluble Hormones

• Amine hormones use amino acids as their base (e.g., epinephrine & norepinephrine).
• Peptide and protein hormones are amino acid polymers (e.g., insulin & glucagon).
• Eicosanoid hormones are derived from arachidonic acid (e.g., prostaglandins & leukotrienes).

Mechanisms of Hormone Action

• Responsiveness depends on hormone concentration, receptor abundance, and influence from other hormones.
• Permissive Effect: Requires simultaneous or recent exposure to a second hormone.
• Synergistic Effect: Combined effect is greater than the sum of individual effects.
• Antagonistic Effect: One hormone opposes the action of another.

Permissive Effect Example

• Epinephrine weakly stimulates triglyceride breakdown alone.
• When with T3 or T4, epinephrine stimulates breakdown more powerfully.

Synergistic Effect Example

• Oocyte development depends on both FSH and estrogens.
• Neither hormone alone is sufficient.

Antagonistic Effect Examples

• Insulin and glucagon.
• PTH and calcitonin.

Hormone Binding and Second Messenger Systems

• Lipid-soluble hormones bind to receptors inside target cells, either in the cytoplasm or in the nucleus, to make RNA, which then makes protein.
• Water-soluble hormones bind to receptors on the plasma membrane, activating a second messenger system, amplifying the original signal.
• cAMP (cyclic AMP) is a common second messenger activating a protein.
• Other second messengers include calcium ions, cGMP, inositol triphosphate (IP3), and diacylglycerol (DAG).

Amplification

• Hormones can induce effects at low concentrations because they initiate a cascade, amplifying the initial effect at each step. A single hormone molecule activates many G-proteins and cAMP molecules, which in turn activate numerous protein kinases, affecting thousands of substrate molecules.

Regulation of Hormone Secretion

• Regulated by signals from the nervous system, chemical changes in the blood, and other hormones.
• Most hormonal regulation occurs through negative feedback.
• Positive feedback examples include oxytocin stimulating uterine contractions.

Hypothalamus and Pituitary Gland

Hypothalamus

• A small brain region below the thalamus.
• Provides the highest level of endocrine function by integrating nervous and endocrine systems.

Pituitary Gland

• A small, oval gland in the sella turcica of the sphenoid bone.
• Attached to the hypothalamus by the infundibulum.
• Anterior lobe (adenohypophysis) derived from glandular tissue, consisting of the pars distalis and pars tuberalis.
• Posterior lobe (neurohypophysis) derived from neural tissue, consisting of the pars nervosa and infundibulum.

Hypothalamic-Pituitary Connection

• The hypothalamus and the anterior pituitary are linked via the hypophyseal portal system (blood).
• The hypothalamus and the posterior pituitary are linked via neural connections.

Hypothalamic Control Over the Endocrine System

• The hypothalamus secretes regulatory hormones that control anterior pituitary gland endocrine cells.
• Hypothalamic neurons synthesize and transport ADH and oxytocin to the posterior pituitary.
• Autonomic centers within the hypothalamus directly stimulate endocrine cells in the adrenal medulla, releasing epinephrine and norepinephrine in response to sympathetic division activation.

Neurosecretory Cells

• Hypothalamic neurosecretory cells make and release hormones.
• Specialized neurons make releasing and inhibiting hormones, packaged into vesicles that reach axon terminals via axonal transport.
• Nerve impulses stimulate exocytosis, and hormones reach the anterior pituitary via the hypophyseal portal system or the posterior pituitary via neurons.

Anterior Pituitary

• Makes and releases 7 hormones.
• These are called tropic hormones because they "turn on" other endocrine glands.
• Release is controlled by hypothalamic releasing and inhibiting hormones and regulated by negative feedback.
• Five cell types release seven hormones:
• Somatotrophs: hGH
• Thyrotrophs: TSH
• Gonadotrophs: FSH and LH
• Lactotrophs: PRL
• Corticotrophs: ACTH and MSH

Somatotrophs

• Secrete human growth hormone (hGH or somatotropin).
• Secretion is controlled by GHRH and GHIH from the hypothalamus.
• hGH stimulates secretion of insulin-like growth factors (IGFs) that promote growth and protein synthesis.

IGF Functions

• Cause cells to grow and multiply by increasing amino acids uptake and stimulating protein synthesis.
• Enhances lipolysis in adipose tissue to allow an increased use of fatty acids for ATP production.
• Decrease breakdown of proteins and glucose uptake to ensure it is available to neurons for ATP production during glucose scarcity.

Thyrotrophs

• Secrete thyroid-stimulating hormone (TSH or thyrotropin).
• Secretion is controlled by TRH from the hypothalamus.
• TSH stimulates the synthesis and secretion of thyroid hormones (T3 and T4) by the thyroid.

Gonadotrophs

• Secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
• Secretion is controlled by GnRH from the hypothalamus.
• FSH initiates oocyte development in women and stimulates sperm production in men controlled by gonadotropin-releasing hormone (GnRH).
• LH triggers ovulation, stimulates the testes to produce testosterone controlled by gonadotropin-releasing hormone (GnRH).
• Both FSH and LH stimulate secretion of estrogen.

Lactotrophs

• Secrete prolactin (PRL).
• Stimulates milk production.
• Secretion is controlled by dopamine (prolactin-inhibiting factor, PIF) and prolactin-releasing hormone (PRH) from the hypothalamus.

Corticotrophs

• Secrete adrenocorticotropic hormone (ACTH or corticotropin) and melanocyte-stimulating hormone (MSH).
• Secretion is controlled by CRH from the hypothalamus.
• ACTH stimulates glucocorticoid secretion by the adrenal cortex regulated by corticotropin-releasing hormone (CRH).
• MSH increases melanin production, with an unclear overall function.

Posterior Pituitary

• Releases two hormones (but makes none), both made in the hypothalamus, which extend from hypothalamus and ends near blood capillaries in posterior pituitary
• These are oxytocin (OT) and antidiuretic hormone (ADH).

Oxytocin (OT)

• Synthesized in the paraventricular nucleus in the hypothalamus.
• Stimulates smooth muscle contraction in the uterus and myoepithelial cells in mammary glands.
• Promotes labor and delivery, and milk ejection.
• Functions in males and non-pregnant individuals are unclear but may have a role in sexual activity, trust, and bonding.

Antidiuretic Hormone (ADH)

• Also known as vasopressin (VP).
• Synthesized in the supraoptic nucleus in the hypothalamus.
• Release is controlled by increases in blood solute concentration or decreases in blood pressure/volume, and inhibited by alcohol.
• Primary function is to act on kidneys to retain water and decrease urination.
• It also causes vasoconstriction to increase blood pressure.

Hormones Summary

• Hypothalamus makes 9 hormones and the Anterior Pituitary makes and releases 7, and the Posterior Pituitary makes 0 and releases 2.
• Hypothalamus releases GHRH, GHIH, TRH, GnRH, PRH, PIF, and CRH to the anterior pituitary.
• Hypothalamus releases OT and ADH from the posterior pituitary.
• Anterior Pituitary releases GH, TSH, FSH, LH, PRL, ACTH, and MSH.
• Posterior Pituitary releases OT, ADH.

Thyroid Gland

Location and Anatomy

• Found on the anterior surface of the trachea, inferior to the thyroid cartilage.
• Composed of two lobes connected by a narrow isthmus.
• Size is variable and can be felt with fingers.

Histology

• Contains many thyroid follicles, which are hollow spheres lined by simple cuboidal epithelium (follicular cells).
• Follicle cavity holds viscous colloid, containing the protein thyroglobulin (TGB), the building block of thyroid hormone.
• Follicles are surrounded by capillaries for nutrient, waste, and secretory product transport. C Cells (parafollicular cells) are found and secrete calcitonin (CT) which regulates calcium ion concentration.

Follicular Cells

• Produce two thyroid hormones:
• Thyroxine or tetraiodothyronine (T4)
• Triiodothyronine (T3)
• Both increase metabolism, stimulate protein synthesis, and increase glucose/ATP production.
• More T4 is produced, but T3 has a greater effect; about 1/3 of T4 is converted to T3 in tissues.

Formation, Storage, and Release of Thyroid Hormone

• The thyroid gland stores its secretory products in large quantities.
• Thyroid hormones are synthesized from iodine and tyrosine, attached to thyroglobulin (TGB), and stored as thyroglobulin in the follicle.
• They are transported in the blood bound to plasma proteins like thyroxine-binding globulins (TBG).

Additional Thyroid Hormone Details

• Iodine ions from diet are delivered to thyroid gland and taken up by follicle cells.
• Enzymes convert iodide ions to iodine atoms and attach them to tyrosine portions of thyroglobulin molecule.
• Thyroxine (T4) and triiodothyronine (T3) are produced and stored in thyroglobulin. Follicle cells remove thyroglobulin from follicle by endocytosis.
• Amino acids are used to synthesize more thyroglobulin. Lysosomal enzymes break down thyroglobulin, releasing thyroid hormones and amino acids into cytoplasm.
• T4 (~90% of thyroid secretions) and T3 (10.5 mg/dL ) --> heart stops–cardiac arrest.
• Hypocalcemia ( respiration stops–respiratory arrest.

Blood Calcium Levels

Calcium Levels

• Adjusted in three locations.
• Bone: Resorption increases blood Ca2+, deposition decreases blood Ca2+.
• Kidney: Increased reabsorption increases blood Ca2+, decreased reabsorption decreases blood Ca2+ on the early distal convoluted tubule.
• Gastrointestinal Tract (small intestine): Increased absorption increases blood Ca2+, decreased absorption decreases blood Ca2+.

Calcium Level Maintenance

• Maintained by three hormones.
• Calcitonin: decreases blood Ca2+.
• Parathyroid Hormone (PTH): increases blood Ca2+.
• Calcitriol: increases blood Ca2+ (activated form of vitamin D).

Calcitonin

• A hormone produced by parafollicular cells (C cells) of the thyroid gland.
• Overall effects: decreases blood calcium, i.e., calcitonin = bone in.
• Has antagonistic effects to PTH and calcitriol.
• Decreases blood calcium by:
• Decreasing bone resorption – puts calcium into bone from the blood
• Inhibiting osteoclasts
• Osteoblasts do not have receptors for calcitonin
• Overtakes osteoclastic activity --> more bone deposited than reabsorbed
• Decreasing kidney reabsorption of calcium leading to an Increase calcium loss in the urine

Parathyroid Hormone (PTH)

• A hormone produced by parathyroid glands.
• Overall effects: increases blood Ca2+.
• Has antagonistic effects to calcitonin and synergistic effects to calcitriol.
• Two cell types:
• Oxyphil cells – no known functions
• Parathyroid (principal) cells
• • Produce parathyroid hormone

PTH Increases Blood Calcium by

• Increasing bone resorption.
• Osteoclastic activity overtakes osteoblastic activity – more bone reabsorbed than deposited
• Increasing osteoclast activity
• Acting on the kidneys.
• Increasing kidney reabsorption of calcium
• Reduced Ca2+ loss in the urine
• Activating calcitriol or vitamin D

Calcitriol

• Hormone made in the epidermis (skin) from a cholesterol precursor activated by UV radiation
• Increases the amount of Ca2+ in the blood
• Overall effects: increases blood Ca2+
• Has antagonistic effects to calcitonin and synergistic effects to PTH

Calcitriol Increases Blood Calcium by

• Acting in the small intestine.
• Increasing intestinal absorption of Ca2+
• Calcium Homeostasis Recap

Hormones Effect on Blood Calcium

• Calcitonin decreases blood Ca2+, decreases bone resorption, and reduces reabsorption in kidney
• PTH increases blood Ca2+, increases bone resorption, increases reabsorption in kidney, and indirectly activates calcitriol in kidney
• Calcitriol increases blood Ca2+ by increasing absorption in the intestines