Human Physiology Final

The Endocrine System

Hormones

• Chemical messengers

• Distant targets

• Travel in the blood → diffuses into blood and travels through body in low concentrations

• Low concentrations

Endocrine cells/glands

• Cells which release hormones

Target tissue (cell)

• Tissues (cells) which contain receptors for that particular hormone

Types of Hormones

Peptide

• made of chains of amino acids

• most diverse group

• ANP, insulin

Steroid

• derived from cholesterol

• smaller group

• “-sterone” suffix

• Aldosterone, progesterone, testosterone, etc

Amines

• derived from tyrosine or tryptophan (single amino acids)

• subgroup: catecholamine → dopamine

• subgroup: thyroid hormone → T3 and T4

Peptide Hormones

Made of peptides

• Preprohormones

• Cleaved to activate

• Hydrophilic

Fast acting, short duration

• Membrane receptors

• 2nd messenger systems, ion channels

Half life = few minutes

• Half life = time until half of the hormone degrades

Steroid Hormones

Lipophilic

• Made when needed, if made in advance, will diffuse out bc permeable

Slow acting, long duration

• Intracellular receptors

• Activate gene transcription

Half-life = minutes to hours

Use protein carriers in the blood to move through the body

• protein carriers protect the hormone from being taken into the wrong cell and metabolized.

Synthetic Pathway of Steroids

• generally: cholesterol → progesterone → corticosterone → aldosterone

• testosterone → estradiol

Amine Hormones

Catecholamines

• epinephrine, norepinephrine

• hydrophilic

• membrane receptors

Thyroid

• T3 and T4

• Hydrophobic

• Intracellular receptors

• regulate metabolism

Hormone Release

Feedback loops

• Mostly negative

• Some positive

Simple (classic)

• Endocrine cell senses and releases hormone which effects another cell

• Multiple stimuli/input: as a result of feedback loops

Complex pathways

• two or more hormones

• Hormone A affects Hormone B affects C…

• Hypothalamic pituitary axis

Hypothalamic Pituitary Axis

Hypothalamus

• Neurocrines- produced by neurons, released into blood

• Hormones

Posterior Pituitary

• Releases hypothalamic neurocrines

• not a true endocrine gland because it does not produce a hormone, but it’s still treated like an endocrine gland

Anterior Pituitary

• Responds to trophic hormones from hypothalamus

• true endocrine gland because it produces and responds to hormones

Hypothalamic Anterior Pituitary

• “-RH” = releasing hormone

• “-IH” = inhibiting hormone

• dopamine = prolactin inhibiting

• somatostatin = growth hormone inhibitor

• “-RH” and “-IH” = hormones released by the hypothalamus

Hormone Interactions

Synergistic (Moyes 3rd ed)

• Two+ hormones affect target

• Results in greater than additive response (not just added)

Permissiveness

• Hormone allows another to be fully active

Antagonistic

• One hormone blocks effects of another

Hormone Pathologies

Secretion

• Hypo-secretion: less/below

• Hyper-secretion: more/above

Receptors

• Up-regulation (more sensitive; hyper-responsiveness)

• Down-regulation (less sensitive; hypo-responsiveness)

Metabolism

• Metabolism – all chemical reactions in body

• Input (food) = Output (work + heat

• Input > Output

• Weight gain

• Glycogen, Fat → long-term energy store, takes longer to release. Short-term energy store, rapidly available

• Input < Output

• Weight loss

Energy Balance

Input

• appetite → tells us when hungry

• satiety → tells us when full/satisfied

Output

• transport work → across membranes

• chemical work → synthesis for growth/maintenance

• mechanical work → movement

• heat

• Social and psychological factors tend to override satiety. why people eat more when they are already full.

Energy Balance and Neural Factors

Neural Factors

• Feeding Center

• - Satiety Center

Hormonal Input

• CCK → released by digestive tract in response to proteins and lipids

• Insulin → released by pancreas in response to high glucose. insulin = carbohydrate

• Leptin → released by adipose tissue

Energy Balance and Theories

Glucostatic Theory: Short-term, meal-by-meal

• Low glucose

• Stimulate feeding center

• Inhibit satiety center

• Satiety center needs insulin

• Relationship to diabetes I: Not enough insulin. Symptom is polyphagia→ eating all the time bc insulin is too low to stimulate satiety center

Lipostatic Theory: long-term, weeks/months

• Low fat stores

• Stimulate feeding center: eat a little extra at each meal → increase lipid stores and increase leptin = stimulate satiety center

• Inhibit satiety center

Measuring Energy Use

Direct Calorimetry

• Why don’t we use this?

• because psychological factors and bigger organisms cause bigger leaks.

• people panic about small spaces → feel like they’re put in a box

O2 consumption

• L_O2/hour x kcal/L_O2

• assumes all rxns are aerobic

• assumes you’re using all O₂ right now for current needs, and none is stored

Respiratory Quotient

• gives estimate of calories an individual is burning

• CO2/O2

• Carbohydrates = 1

• Proteins = 0.8

• Fats = 0.7

Metabolic Rate Factors

Basal Metabolic Rate

• Taken while resting/fasting. must be awake.

• Age (younger): 5 year old has a higher rate than a 60 year old bc lower body mass and lots of energy is being used for growing

• Gender (males): males generally have higher rates than females

• Lean Muscle Mass (more): more lean muscle = higher metabolic rate

• Hormones

Resting Metabolic Rate

• taken when awake and not fasting

Metabolism

• Activity level (more): high rate

• Diet induced thermogenesis (proteins): creating heat = high metabolism. proteins take more energy to digest

Temperature Homeostasis

Temperature increase

• Exercise

• Diet induced

• thermogenesis

• Circadian rhythms

• Hormonal cycles

• Environment

Temperature decrease

• Environment

Regulation of Temperature

Increase or decrease

• Blood flow

• Behavioral adaptations

Decrease

• Sweating

Increase

• Shivering

Regulation and Set Point

Set Points

• Increase → fever

• Decrease → hot flash

Imbalances → no longer in set point range

• Too hot

• Heat exhaustion → sweating increases, red skin, lightheadedness/fainting, barely above setpoint

• Heat stroke → no longer sweating, temp rapidly increases, delirious

• Malignant Hyperthermia → can’t signal correctly to maintain homeostasis

Too cold

• Hypothermia: can start at 70 degrees

Metabolism: Fed/Absorptive State

• Energy: (carbohydrates)

• Synthesis (proteins) → repair, rebuilding, synthesis

• Storage (fats and carbohydrates) → excess carbs go to storage

• Storage = glycogenesis: glucose → glycogen

• Synthesis: glycogenolysis: glycogen → glucose

Metabolism: Fasted/Post-Absorptive State

Catabolic Reactions: breaking down

• which rxns release energy?

• glycogenolysis: glycogen → glucose

• lipolysis

• protein degradation → only occurs during prolonged fasting

Anabolic reactions

• Gluconeogenesis: production of new glucose

• breaking down lipids and proteins to make glucose

• mostly used by brain

Metabolism Overview (Image)

Control of Metabolism: Hormones

• Pancreatic Hormones

Insulin → released in fed state

• Decreases glucose levels

• Promotes anabolic reactions → synthesis/building

Glucagon → released in hungry state

• Increases glucose levels

• Promotes catabolic reactions

Insulin Stimuli

• Increased Glucose Concentrations

• Increased Amino Acid Concentrations

• GIP Secretion: Glucose-dependent Insulinotropic Peptide

• Parasympathetic Stimulation → Sympathetic Division inhibits

• Glucagon-like Peptide 1 (GLP-1) Secretion

• released by small intestine when glucose is in GI tract

• if glucose is in intestine, it will be a short time before it’s in the blood.

Mechanism of Insulin’s Effects

• The brain (with exception of satiety center) doesn’t require insulin to take up glucose

• if exercising, it causes skeletal muscle to insert glucose transporters

Glucagon

Antagonist to insulin

Increases glucose

• Glycogenolysis

• Lipolysis

• these two release stored energy

• Gluconeogenesis: uses breakdown products of lipids and proteins to make glucose

• under starvation conditions, breaks down proteins

Type I Diabetes Mellitus

• not enough insulin production

• polyphagia: always hungry bc no stimulus going to satiety center

• polyuria: frequent urination → glucose pulls water out of urine, increasing blood osmolarity

• polydipsia: always thirsty → increasing blood osmolarity bc increased blood sugar and decreased volume due to frequent urination.

• decreased blood pressure and blood volume causes decreased circulation = coma or death

Phases of Digestion

• focus on hormone productions in each phase

Cephalic

• It’s all in the head

Gastric

• Food in stomach

Intestinal

• Food in intestines

Motility, secretion, digestion, and absorption for each phase

Gastric Phase: Stimuli and Effects

Stimuli

• Peptides or amino acids in stomach, stretch, signals from CNS (cephalic phase)

Effects

• Increased motility

• Increased secretion of enzymes and hormones

Gastric Phase: Motility and Secretions

Motility:

• Peristalsis and movement of food to intestines

• Pyloric valve /sphincter

Secretions

• Acid, intrinsic factor

• Pepsinogen (proteins), gastric lipase (fats) ← enzymes

• Somatostatin (hormone: inhibits acid secretion)

• Gastrin (hormone: stimulates acid secretion) → causes protein degradation making them easier to digest

• mucus and bicarbonate: protects stomach from acid (buffer

Gastric Phase: Digestion and Absorption

Digestion

• Proteins (acid, pepsin)

• Fats (gastric lipase)

Absorption

• Alcohol, Lipophilic drugs (aspirin): rate of alcohol consumption and % alcohol affect absorption because they create a concentration gradient

• Very small amounts of water

Intestinal Phase: Stimuli and Effects

Stimuli

• Fats, amino acids, carbohydrates, or acid in intestine

Effects

• Increased motility

• Increased secretion of enzymes and hormones

Intestinal Phase: Secretion and Enzymes

Secretion

• from intestinal wall, pancreas, and liver

Enzymes

Intestine (brush border enzymes):

• peptidases

• disaccharidases

• enteropeptidase

Pancreas:

• pancreatic amylase

• lipase

• proteases

• carboxypeptidase and aminopeptidase

Other Digestive Secretions

• Intestine: mucus, bicarbonate

• Pancreas: bicarbonate

• Liver: bile (stored in gallbladder as well)

Intestinal Phase: Secretions

• Intestinal Hormones

• need to know hormone: stimulus: effect

• Cholecystokinin (CCK): fatty and amino acids; stimulates pancreatic enzyme release, contractions of gall bladder.

• digests fats/proteins and gallbladder releases bile to help digest fats

• Secretin: acid in intestine; stimulates bicarbonate release, inhibits gastrin

• Glucose-dependent insulinotropic peptide (GIP): glucose, fatty and amino acids; stimulates insulin release, may inhibit acid release

• Motilin: fasting; stimulates migrating motor complex

Intestinal Phase; Digestion and Absorption

Proteins

• Proteases: Trypsin, Chymotrypsin, and peptidases

• Amino acids, di and tri-peptides

• Transporters absorb larger 3 aa peptides whole via transcytosis after binding to membrane receptors on luminal surface of intestine

• Link to newborns and food allergies + immunity bc peptides may act as Ag. If parents delay feeding their infant allergy-inducing peptides, gut has chance to mature, reducing chance of allergy.

Fats/Lipids → 2nd image

• Bile: amphipathic → hydrophobic portion interacts with the surface of lipids and polar side chains interact with water to create water-soluble droplets

• Lipase: breaks down triglycerides into a monoglyceride and 2 fatty acid chains

• Colipase: lipase can’t penetrate bile salt. Colipase is secreted by the pancreas and acts as a cofactor that displaces bile salts, allowing lipase access to fats inside the bile salt coating.

• Free fatty acids and monoglycerides → absorbed via simple diffusion

• Multiple stages for digestion

• Absorbed by diffusion

Adrenal Glands

Adrenal Cortex

• Outer – aldosterone

• Middle – glucocorticoids

• Inner – sex hormones

Adrenal Medulla

• Catecholamines

Cortisol

• Hypothalamus: secretes CRH (corticotropin-releasing hormone), which is transported to A. Pituitary.

• A. Pituitary: secretes ACTH (adrenocorticotropin hormone), stimulates adrenal cortex to synthesize and release cortisol

• Adrenal Cortex: produces Cortisol, which acts in a negative feedback loop to inhibit CRH and ACTH

Effects of Cortisol

• Gluconeogenesis: in liver. Some glucose produced in liver is released into the blood and the rest is stored as glycogen → prevents hypoglycemia

• Catabolism of skeletal muscle: breaks down skeletal muscle proteins to provide substrate for gluconeogenesis

• Lipolysis: enhances lipolysis so fatty acids are available to peripheral tissues for energy. Glycerol from the fatty acids is used for gluconeogenesis

• Suppress immune system: inhibits release of cytokines and blocks Ab production by wbc’s. Decreases inflammatory response by inhibiting leukocyte mobility. Immunosuppressant → treats inflammation from bee stings, poison ivy, etc, and is effecting in preventing transplant rejection

• Catabolism of bones: decreases intestinal Ca²⁺ absorption, increases renal Ca²⁺ excretion = net Ca²⁺ loss. Cortisol causes net breakdown of calcified bone matrix. People who take therapeutic cortisol for long periods have higher frequency of broken bones

• Permissive for glucagon and epinephrine: because it’s required for full glucagon/catecholamine activity.

What happens if you take cortisol blockers?

• can treat Cushing Syndrome (hypersecretion of cortisol)

• reduced gluconeogenesis → hypoglycemia

• decreased vasoconstriction → low bp

• increased inflammation and autoimmune flare-ups due to reversed immunosuppression

• disrupt sleep

Cortisol Loop and Circadian Rhythm

Cortisol follows a strict 24-hour circadian rhythm, peaking roughly 30–45 minutes after waking (the Cortisol Awakening Response, or CAR) to promote alertness and hitting its lowest point around midnight.

Effects of T₃ and T₄ (Thyroid Hormones)

In Fetus and early childhood

• Full expression of GH

• Normal growth

• Development of neural system

Affect metabolic rates (all ages)

• Increases metabolism and heart rate

Thyroid Hormone Loop

• Hypothalamus: TRH → thyrotropin releasing hormone. controls release of A. Pituitary hormone thyrotropin or TSH

• A. Pituitary: TSH → Thyroid-stimulating hormone. acts on thyroid gland to promote synthesis of T₃ and T₄

• Thyroid Gland – T3 and T4 → act as negative feedback and inhibit TRH and TSH to prevent hyper-secretion

Growth Hormone Loop

• Hypothalamus – GHRH, SS (GHIH)

• A. Pituitary – GH

• Affects growth of tissues, bones

• Causes release of insulin-like growth factors

• Cortisol – catabolic reactions releasing energy

• Growth Hormone – anabolic reactions (building and repairing)

Growth Hormone Pathophysiologies

• Dwarfism: Severe growth hormone deficiency in childhood, resulting from problem with GH synthesis or defective GH receptors

• Giantism: over-secretion of growth hormone in children. Bone growth stops in late adolescence, but GH can still act on cartilage and soft tissues

• Acromegaly: adults with excessive GH secretion causing lengthening of jaw, coarsening of facial features, and growth of hands and feet.

Hormonal Regulation

Anti-diuretic hormone / Vasopressin

• Water balance

Aldosterone

• Na+, K+ Balance (and water)

Atrial Natriuretic Peptide (ANP)

• Na+ Balance (and water)

Parathyroid Hormone (PTH) and Calcitriol (D)

• Ca2+ Balance

Calcium Balance and Loop

Parathyroid Hormone

• Increases Calcium levels

• Bone, Kidney, Intestine

Calcitriol (vitamin D)

• Reinforces PTH effects

Calcitonin

• Decreases Calcium Levels

• Bone, Kidney

Reproduction

Sex Determination
• 22 matched pairs of chromosomes
• 1 pair sex chromosomes
• XX- female
• XY- male
• X is required for survival

Sexual Differentiation

Male

• SRY gene present

• Encodes testes determining factor

• Testes secrete:
  • Mullerian inhibiting substance
  • Testosterone and DHT

• Wolffian (mesonephric) ducts converted

Female

• No SRY gene

• Mullerian (Paramesonephric) ducts form vagina, uterus, fallopian tubes

• External genitalia become female

Gametogenesis

• Males- sperm

• Females – oocytes

• Mitosis occurs in embryo for both

• Mitosis = 2 identical cells → builds population of cells for division

• Each gamete contains one sex chromosome

Gametogenesis: Male

• Mitotic division starts again at puberty to ensure there are enough primary spermatocytes to produce 100 mil sperm/day as adult

• All stages of meiosis occur as adult

• Reproductive adult

• Takes about 2 months

• 100 million sperm/day → part of reason for high metabolism in males, lots of energy is dedicated to sexual reproduction

• one primary spermatocyte produces 4 sperm

Gametogenesis: Female

Embryo

• Mitosis

• Meiosis I started (prophase I pause)

• when females are born, they will have all of the primary oocytes they will need for the rest of their lives

Reproductive Adult

• Meiosis I finishes (1 per month

• Secondary oocyte released

• Meiosis II starts (pauses in metaphase)

Fertilization

• Meiosis II finishes

• primary oocyte produces 1 egg and polar bodies

• polar bodies = very small cells with half DNA, only purpose of polar body is to take ½ DNA from egg

• the egg produced is very large bc it needs to have all resources for development

Gametogenesis Differences Between Males and Females

Males

• Mitosis in embryo and adult

• Meiosis continuous in adult

• 100-200 million/day

• 4 sperm/primary gamete

• 34-35°C → below body temperature, which is why testes descend to be on outside of the body to allow enzymes to function at the cooler temperature for spermatogenesis

Females

• Mitosis in embryo only

• Finishes only with fertilization

• 1/month

• 1 oocyte + 2 (3) polar bodies/gamete

• 37°C

Hormone Control Loop (Image)

Male Control Loops

• GnRH – stimulates FSH and LH

• LH → Stimulates Leydig (interstitial) cells to produce testosterone (inhibits GnRH and LH)

• FSH → Stimulates Sertoli (nurse, sustentacular) cells to produce sperm and Inhibin

• Hormones released in pulses

• Circadian Rhythms

• Testosterone

• Secondary sex characteristics

• forms small amounts of estrogen

• Why do synthetic androgens cause sterility? Because high testosterone inhibits GnRH and LH, preventing spermatogenesis

What would excess secretion (hyersecretion) of TSH result in?

• increased secretion of T3 and T4

• decreased secretion of TRH

• increased metabolic rates

Calcium Balance Feedback loop

• The receptor (chemoreceptor), afferent pathway (2nd messengers), and integrating center (parathyroid cell) are all located within the endocrine cell

• the efferent pathway = parathyroid hormone

• effector = bone (release Ca²⁺), kidney (reabsorb Ca²⁺), and GI tract (absorb Ca²⁺)

What are two characteristics that are true for an endocrine feedback loop but NOT a neural loop?

• multiple effectors can be stimulated by a single signal

• the first three parts of the feedback loop are contained in a single cell

Why is the posterior pituitary gland not a true endocrine organ?

it does not produce a hormone

Hormones which have long half-lives, utilize intracellular receptors, and are slow-acting may belong to the group known as:

Steroid hormones (e.g., cortisol, aldosterone, sex hormones) are lipid-soluble, so they:

• Diffuse across cell membranes

• Bind intracellular (cytoplasmic or nuclear) receptors

• Directly influence gene transcription

This leads to:

• Slow onset of action (requires protein synthesis)

• Long half-lives (circulate bound to carrier proteins, reducing degradation)

How do insulin and cortisol act as an antagonistic pair?

• Insulin lowers blood glucose by promoting uptake and storage (glycogenesis, lipogenesis).

• Cortisol raises blood glucose by promoting gluconeogenesis and reducing glucose uptake in tissues.
  → These effects directly oppose each other.

What could an increase in ACTH cause?

Gluconeogenesis

• ACTH (adrenocorticotropic hormone) stimulates the adrenal cortex to release cortisol.

• Cortisol is a catabolic hormone that:

  • Increases gluconeogenesis in the liver

  • Promotes protein breakdown (not synthesis)

  • Promotes lipolysis rather than lipogenesis

What could cause low levels of Calcium?

Hypersecretion of calcitonin

• Calcitonin lowers blood calcium by:

  • Inhibiting osteoclast activity (less bone resorption)

  • Increasing calcium deposition in bone
    → Excess calcitonin can decrease blood Ca²⁺ levels

What makes an endocrine loop simple?

• The use of only one hormone

• In a simple endocrine reflex, a single endocrine gland both senses the stimulus and secretes the hormone.

• There’s no hypothalamus–pituitary cascade involved.

What is the order of events for the male hormone feedback loop?

1. Release of GnRH

2. Secretion of LH increases

3. Gonads increase secretion of testosterone/estrogen/progesterone

4. Elevated levels of T/E/P create feedback

5. GnRH and LH levels decrease

What hormone inhibits FSH?

inhibin, produced by the sertoli cells

What is the relationship between estrogen levels, receptors, and responses

higher levels of estrogen are able to bind to receptors with lower affinity for estrogen, stimulating the release of more GnRH and LH

What are the order of events for the female hormone loop?

1. elevated levels of estrogen stimulate GnRH and LH

2. LH surge causes ovulation of the oocyte

3. LH causes the remainder of the follicle to form the corpus lutetium

4. Corpus luteum releases progesterone, inhibin, and estrogen

5. Progesterone, inhibin, and estrogen inhibit GnRH, LH, and FSH while waiting to see if pregnancy occurs

When is chorionic gonadotropin released? What does it do?

• after implantation occurs and the placenta forms → placenta releases chorionic gonadotropin

• human chorionic gonadotropin causes growth of the corpus luteum

Female Control Loops: GnRH, LH, FSH

GnRH- stimulates FSH and LH

LH

• Stimulates thecal cells

• Forms corpus luteum (along with granulosa)

• Peak – ovulation

FSH

• Follicle development and granulosa (follicle) cells

• Granulosa cells produce estrogen, inhibin

Female Control Loops: Estrogen/Estradiol

Estrogen (Estradiol)

• Produced primarily by follicle and at lower amounts by the Corpus luteum

• Builds endometrium → layer where implantation occurs

• Inhibits GnRH at low levels

• Stimulates GnRH at sustained high levels

• Secondary sex characteristics (androgens help)

How can positive and negative feedback of GnRH occur with Estrogen?

• the key is receptors → determine how cells and tissues respond to hormones

Female Control Loops: Progesterone

Progesterone

• Produced primarily by corpus luteum and in lower amounts by follicle

• Maintains endometrium with high levels

• Inhibits GnRH

Inhibin – inhibits FSH

Female Control Loops: Hormonal Cycle

Menses

• low progesterone causes shedding of lining

• high FSH causes shedding of lining to start over and create a new follicle

Proliferative Phase

• high estrogen level → pos. feedback to LH

• surge in LH triggers ovulation

Secretory Phase

• high progesterone → inhibits GnRH, FSH, and LH

• high inhibin → inhibits GnRH, FSH, and LH

• oocytes have 24 hours to be fertilized before th hormones drop and the corpus luteum dissolves

Procreation: Males

Pathway for Sperm

• Seminiferous Tubules

• Epididymis

• Vas (Ductus) Deferens

• Urethra

• Prostate = joining point of urinary tract and sexual fluid

Composition of Semen

• Sperm – gamete

• Water – travel medium

• Mucus – lubrication → holds sperm in clump

• Bicarbonate – buffer → vagina is acidic, it slows the change in pH

• Nutrients – cell survival, sperm live 5-6 days in a female

• Prostaglandins → motility in the female tract

• Glands: Seminal Vesicles, Prostate Gland, Bulbourethral Gland

Procreation in females

Pathway for Ova/Eggs

• Ovary

• Fallopian (Uterine) Tubes/(Oviducts)

• Fertilization

• Uterus

Pregnancy

• Implantation in uterus

• Ectopic and Tubal → tubal is most common. Ectopic is any implantation outside the uterus