physio

MODULE 8: ENDOCRINE PHYSIOLOGY

PARTIAL LIST OF ENDOCRINE GLANDS

  • Pineal gland

  • Pituitary gland

  • Hypothalamus

  • Thyroid gland

  • Adrenal gland

  • Pancreas

  • Ovary

  • Testis

Hormone Basics

Definition of Hormones

A hormone is defined as a signaling molecule that travels through the bloodstream.

Composition of Hormones

Hormones can be made of different types of molecules:

  1. Amines: Derived from amino acids.

    • Example: Thyroid hormone (TH), Epinephrine (Epi)

  2. Polypeptides: Chains of amino acids.

    • Example: Insulin, Growth Hormone (GH), Antidiuretic Hormone (ADH)

  3. Glycoproteins: Proteins that are glycosylated (have carbohydrate groups).

    • Example: Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH)

  4. Steroids: Lipid-based hormones, typically derived from cholesterol.

    • Example: Estrogen, Progesterone, Testosterone, Cortisol

Mechanisms of Hormone Action

How Hormones Work

Hormones exert their effects by binding to receptors on or inside target cells. The cellular responses can vary based on several factors:

  • Synergistic effects: An additive or complementary response when tissues are acted on by more than one hormone.

  • Permissive effects: One hormone enhances the target tissue's response to a second hormone.

  • Antagonistic effects: One hormone decreases the responsiveness of a tissue to another hormone.

  • Saturation: A state in which there are enough hormone molecules available such that nearly all receptors are bound.

  • Up and down regulation: Mechanisms that increase (upregulation) or decrease (downregulation) the number of receptors in response to hormonal exposure can occur, leading to desensitization of the receptors.

Target Tissues

Any cell with receptors for a certain hormone is considered a target tissue.

Hormone Release and Transport

Hormone Release

Hormones are stimulated to be released through various mechanisms:

  1. Filtering: Hormones can be filtered by the kidneys.

  2. Degradation: Once released, hormones can degrade in the bloodstream or be broken down inside target cells (particularly lipid-soluble hormones).

Types of Hormones

  • Water-soluble hormones: These hormones travel freely in the bloodstream.

  • Lipid-soluble hormones: These hormones often require carrier proteins for transport in the bloodstream.

Common Second Messengers

The actions of hormones are often mediated by second messengers. If a regulator is polar (water-soluble), common second messengers include:

  • Cyclic Adenosine Monophosphate (cAMP)

  • Calcium ions (Ca²+)
    If a regulator is nonpolar (lipid-soluble), its action does not generally require second messengers.

Cell Responses to Hormones

Lipid-Soluble Hormones

Lipid-soluble hormones (such as steroid and thyroid hormones) exert their effects through intracellular receptors. The process includes:

  1. Diffusion: The lipid-soluble hormone diffuses through the plasma membrane.

  2. Receptor Binding: It binds with its receptor in the cytoplasm, forming a receptor-hormone complex.

  3. Nuclear Entry: The complex enters the nucleus and triggers gene transcription.

  4. Protein Synthesis: Transcribed mRNA is translated into proteins that alter cell activity.

Water-Soluble Hormones

Water-soluble hormones bind to membrane-bound receptors and initiate a signaling cascade as follows:

  1. The water-soluble hormone binds to a receptor on the cell membrane.

  2. This binding activates a G protein.

  3. The activated G protein activates adenylyl cyclase.

  4. Adenylyl cyclase catalyzes the conversion of ATP to cAMP.

  5. cAMP serves as a second messenger that activates protein kinases.

  6. Protein kinases phosphorylate proteins in the cytoplasm, activating them to alter cell activity.

Hypothalamus and Pituitary Gland

Overview

The hypothalamus plays a key role in the endocrine system, regulating the release of pituitary hormones. The pituitary gland consists of:

  • Anterior lobe (adenohypophysis): Contains parts like pars tuberalis and pars distalis.

  • Posterior lobe (neurohypophysis): Functions to store hormones such as Antidiuretic Hormone (ADH) and Oxytocin (OT), both of which are synthesized in the hypothalamus.

Posterior Pituitary Hormones

  1. ADH (Antidiuretic hormone)

    • Target: Kidneys, sweat glands, circulatory system

    • Effects: Maintains water balance and osmotic pressure of blood.

  2. Oxytocin (OT)

    • Target: Female reproductive system

    • Effect: Triggers uterine contractions during childbirth.

Anterior Pituitary Hormones

The anterior pituitary produces several hormones relevant to the reproductive system and metabolism:

  1. Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH)

    • Target: Reproductive organs

    • Effects: Stimulate production of gametes (sperm and eggs) and sex hormones.

  2. Thyroid-Stimulating Hormone (TSH)

    • Target: Thyroid gland

    • Effects: Stimulates release of thyroid hormones which regulate metabolism.

  3. Growth Hormone (GH), regulated by GHRH and inhibited by GHIH.

  4. Prolactin (PRL), stimulated by PRH and inhibited by PIH.

  5. Adrenocorticotropic Hormone (ACTH), stimulated by CRH, promotes regulation of glucocorticoid hormone production in response to stress.

Feedback Mechanisms

The release of hormones generally follows a general feedback loop:

  • Hypothalamus releases regulatory hormones.

  • Anterior pituitary releases tropic hormones.

  • Peripheral gland releases peripheral hormones.

  • Target cells ultimately respond, influencing physiological processes including hormonal feedback inhibition to maintain homeostasis.

Adrenal Gland

Structure and Function

The adrenal gland consists of:

  • Adrenal cortex: Produces hormones like mineralocorticoids and glucocorticoids.

    • Mineralocorticoids (e.g., Aldosterone): Regulates ion concentrations in kidneys

    • Glucocorticoids (e.g., Cortisol): Regulates metabolism and stress response

  • Adrenal medulla: Secretes epinephrine and norepinephrine in response to stress.

Stress Response

The body has mechanisms for responding to both acute and chronic stressors:

  1. Acute Stress

    • Triggered by immediate stress impacting the adrenal medulla.

    • Involves sympathetic nervous system activation that leads to secretion of epinephrine.

  2. Chronic Stress

    • Hypothalamus releases CRH, leading to ACTH release from the anterior pituitary, stimulating cortisol release from the adrenal cortex.

  3. Effects of Cortisol:

    • Increases fuel in the blood while inhibiting inflammatory responses and non-essential functions (e.g., reproductive growth).

    • Cushing's Syndrome: Resulting from excessive cortisol production.

    • Addison’s Disease: Resulting from insufficient cortisol production.

Effect of Epinephrine

Epinephrine also affects body responses during stress by achieving the following:

  • Promoting glycogen and fat breakdown, providing rapid sources of energy.

  • Increasing cardiac function, lung ventilation, and redirecting blood flow to skeletal muscles, enhancing muscle performance.

Thyroid Hormone

Metabolic Rate Control

  • The release of thyroid hormones (T3 and T4) is regulated via feedback mechanisms involving TRH and TSH.

  • Elevated levels of T3 and T4 inhibit the release of TRH and TSH.

  • Effects of Thyroid Hormones:

    • Increase the basal metabolic rate of body cells, contributing to thermogenesis (calorigenic effect).

    • Facilitates carbohydrate uptake from the intestinal tract.

    • Exhibits permissive effects on growth hormone and fatty acid release due to epinephrine.

Disorders of Thyroid Hormone

  1. Hypothyroidism: Conditions like iodine deficiency and autoimmune disorders (e.g., Hashimoto's Thyroiditis) leading to insufficient thyroid hormone production.

  2. Hyperthyroidism: Conditions like Graves' disease where excessive thyroid hormone is produced due to autoimmune attacks on the thyroid.

Evaluating Endocrine Disorders

Diagnostic Tests

  • Blood tests are performed to determine hormonal levels:

    1. High serum total T3 indicates potential hyperthyroid conditions.

    2. TSH levels that are not responding to negative feedback indicate gland issues.

Mechanisms of Feedback

  • The endocrine disorder can be determined based on whether pituitary and peripheral gland hormones both trend upward or downward simultaneously or act oppositely, indicating possible gland dysfunction.

Blood Glucose Regulation

Pancreatic Hormones

  • The pancreas regulates blood glucose via the action of insulin and glucagon produced by pancreatic islets:

    • Insulin: Released in response to high blood glucose, facilitating glucose uptake by cells (skeletal muscle, liver, adipose tissue).

    • Glucagon: Released in response to low blood glucose, promoting glycogenolysis and gluconeogenesis when fasting.

Effects of Insulin Deficiency

  1. Diabetes Mellitus: Marked by hyperglycemia (high blood glucose levels) due to inadequate insulin production or action.

    • Type 1 Diabetes: Autoimmune attack on pancreatic B cells, leading to insulin deficit.

    • Type 2 Diabetes: Insulin resistance where target cells do not respond adequately to insulin.

  2. Results of Untreated Diabetes:

    • Increased plasma glucose and fatty acids, osmotic diuresis, leading to dehydration, acidosis, and potentially resulting in coma or death.

Reproductive Endocrinology

Hormonal Control of Reproductive Processes

  • The onset of puberty prompts the hypothalamus to release GnRH, which stimulates the anterior pituitary to release FSH and LH, resulting in sex steroid production by gonads.

Reproductive Function of the Testes

  1. Spermatogenesis: Development and maturation of sperm in seminiferous tubules under the influence of FSH and testosterone.

  2. Hormonal Feedback: Testosterone regulates sperm production via negative feedback mechanisms.

Effects of Testosterone

  • Influences growth and development of male reproductive structures, secondary sexual characteristics, and overall anabolic effects such as muscle and bone growth.

Reproductive Function of the Ovaries

  1. Ovarian Follicle Development: Hormonal cycling leads to maturation of ovarian follicles, with estrogen secreted to prepare for ovulation.

    • Corpus Luteum: Post-ovulation, produces progesterone to maintain the uterine lining.

  2. Menstrual Cycle Phases:

    • Follicular Phase: Estrogen leads to increased FSH sensitivity for follicle maturation.

    • Ovulation Phase: Triggered by an LH surge that causes the release of the egg.

    • Luteal Phase: Progesterone and estrogen levels rise; if no fertilization occurs, hormone levels drop leading to menstruation.

Hormonal Effects in the Female Body

  1. Estrogen: Regulates ovarian function, promotes growth characteristics like breast development and fat deposition.

  2. Progesterone: Prepares the uterus for potential implantation and influences breast tissue.

Pregnancy Hormones

  1. Human Chorionic Gonadotropin (hCG): Maintains corpus luteum production of progesterone during early pregnancy.

  2. Progesterone and Estrogen Levels: These hormones promote uterine growth and maintenance during pregnancy, indicating ongoing viability.