BMS 300- Exam 2

Mechanisms of intercellular communication

1. Exchange of ions and molecules between adjacent cells (of the same type) across gap junctions

2. Chemical signals transfer information from cell to cell

   within a single tissue. Example: blood clot formation

3. Messages affect the same cells that secrete them

4. Hormones are transported to target cells in the bloodstream

Hormone

Is more broadly defined as any chemical, irrespective of whether it is produced by a special gland or not, for export or cellular use, that "controls and regulates the activity of certain cells or organs

Direct communication

Exchange of ions and molecules between adjacent cells (of

the same type) across gap junctions

Paracrine Communication

Chemical signals transfer information from cell to cell within a single tissue. Example: blood clot formation

Autocrine Communication

Messages affect the same cells that secrete them

Endocrine Communication

Hormones are transported to target cells in the bloodstream

Endocrine vs. Exocrine glands

Both are made up of glandular epithelium

Exocrine glands release their contents through a duct that leads to the epithelial surface (Reaches the external environment of the body)

• Merocrine

• Apocrine

• Holocrine

Merocrine

Part – release by exocytosis (sweat & salivary glands)

• Saliva and watery sweat (mere water)

Apocrine

Away – release by part of the cells is pinched off (mammary & odorous sweat glands)

• Milk and odorous sweat, (smelly ape)

Holocrine

Whole – release by entire cell rupturing (sebaceous glands)

• (Hair and holes from acne)

Sebaceous glands are examples of ____ exocrine glands because the entire cell ruptures to release the secretion.

Holocrine

Amino acid derivatives

Hormone being made from a single amino acid

• Tryptophan → Melatonin

• Tyrosine → Thyroid hormones (hydrophobic) vs. Catecholamines (Epinephrine & Norepinephrine) (hydrophilic)

Peptide hormones

Amino acids linked together

• Peptides (2-50 amino acids (a.a) vs. protein hormones (>50 a.a)

Lipid derivatives

• Fatty acid molecules

• Steroid hormones - derived from cholesterol

  • Include androgens from the testes in males

  • Estrogens and progesterone from ovaries in females

  • Corticosteroids from adrenal cortex

  • Calcitriol from kidneys

• Bound to specific transport proteins in the plasma

  • Remain in circulation longer than peptide hormones

Catecholamines and peptide hormones mechanism of action

• Not lipid soluble

• Unable to penetrate plasma membrane

• Bind to receptor proteins on outer surface of plasma membrane (extracellular receptors

Steroid and thyroid hormones

• Lipid soluble

• Diffuse across plasma membrane and bind to receptors inside cell (intracellular receptors)

Hormones derived from ____ are most likely capable of diffusing across plasma membrane and binding to receptors inside cell.

Lipids

G protein coupled receptors

• A hormone that binds to receptors in the plasma membrane cannot directly affect the activities inside the target cell.

• Instead, the hormone uses an intracellular intermediary to bring about its effects.

• Once activated, many G proteins increase cyclic AMP levels, which acts as the second messenger within the cell.

Effects of secondary messengers (G-protien receptors) activation

• The activation of enzymes or opening ion channels may accelerate the metabolic activity of the cell.

  • E.g. Epinephrine and norepinephrine, Calcitonin, Parathyroid hormone, ADH, ACTH, FSH, LH, TSH

Effects of secondary messengers (G-protien receptors) inhibitory effect

• In some instances, G protein activation can decrease cAMP levels in the cytoplasm resulting an inhibitory effect on the cell.

  • E.g. Epinephrine and norepinephrine

GPCR – 7-pass transmembrane receptor pathway

• ligand binding extracellular side causes conformational change

• alpha subunit of GTP binding protein binds intracellular GPCR

  • alpha subunit is inactive with GDP

• GDP released, GTP binds

  • alpha subunit is active with GTP

• activated alpha subunit separates from beta and gamma subunits

  • Gαs

  • Gαi

  • Gαq

G-alpha-s (Gαs ) and G-alpha-i (Gαi ) pathways are both mediated by

cAMP/PKA

• Both subunits bind adenylyl cyclase

G-alpha-s (Gαs) is ___

Stimulatory

• Excites adenylyl cyclase and increases cAMP/PKA

• Adenylyl cyclase converts ATP to cAMP

G-alpha-i (Gαi ) is ____

Inhibitory

• Inhibits adenylyl cyclase and decreases cAMP/PKA

G-alpha-q (Gαq ) pathway

IP3/Ca2+

• Alpha subunit binds Phospholipase C (PLC)

  • Converts PIP2 to IP3 and DAG

  • IP3 binds intracellular calcium store

    • Releases calcium into cytoplasm

    • Increased intracellular calcium causes smooth muscle contraction

Which of the following will need to use a 2nd messenger to activate cellular targets?

Epinephrine

When eipinephring binds to a G-protein coupled receptor, a mutation in ____ may prevent the release of intrercellular Ca2+.

G alpha q

Transport and inactivation of hormones

• Hormones may circulate freely or travel bound to special carrier proteins (if lipid soluable)

• Bloodstream contains a substantial reserve of bound hormones (long life span)

Free hormones

Remain functional for less than an hour and are inactivated when they

1. Diffuse out of bloodstream and bind to receptors on target cells (can diffuse more easily than bound cells)

2. Are absorbed and broken down by liver or kidneys, or

3. Are broken down by enzymes in blood or interstitial fluids

• Thyroid and steroid hormones remain functional much longer

Hormones and intracellular receptors – Genomic effects

• Has an impact of DNA and protein synthesis

• Steroid hormones can alter rate of DNA transcription in nucleus

• Alterations in synthesis of enzymes or structural proteins

  • Directly affect activity and structure of target cell

Hormones and intracellular receptors – Non-genomic effects

• Can bind directly to mitochondria to increase ATP production

• Thyroid hormones bind to receptors within nucleus and on mitochondria

  • Activate genes or change rate of transcription

  • Increase rates of ATP production

Down-regulation

When levels of a particular hormone are high, cells become less sensitive to it by decreasing the number of hormone receptors

Up-regulation

When levels of a particular hormone are low, cells become more sensitive to it by increasing the number of hormone receptors

Hormone release can be triggered by

• Hormonal stimuli

• Humoral stimuli

• Neural stimuli

Hormonal Stimulus

• Arrival or removal of hormone

• The hypothalamus secreates hormones that stimulate the anterior pituitary gland to secreate hormones that stimulate other endocrine glands to secrete hormones

  • Thyroid gland

  • Adrenal cortex

  • Gonad (Testis)

Humoral Stimulus

• Refering to body fluids

• Change in extracellular fluid concentration

• Capillary blood contains low concentration of Ca2+ which stimulates secreation of parathyroid hormone (PTH) by parathyroid glands

Neural Stimulus

• Neurotransmitters

• Preganglionnic sympathetic fibers stimulate adrenal medulla cells to secreate catecholamines (epinephrine and norepinephrine)

  • CNS

  • Medulla of adrenal gland

A protein contains a DNA binding domain and a hormone binding domain. Which of the following is likely true about this protein.

It can be synthesized on free ribosomes since it is mostly hydrophillic it is comfortable in the cytoplasm

Secretes

Something that is made and then released

Released

Just letting out what “somone” else made

Pituitary gland

Hangs inferior to hypothalamus

• Anterior lobe has three regions (produces & secretes 7 hormones) – ACTH, TSH, GH, PRL, FSH, LH, MSH

• Posterior lobe (releases 2 hormones) – OXT, ADH

Hypophyseal Portal System

• Ensures that regulatory hormones reach cells in anterior pituitary before entering general circulation (unidirectional flow)

• Both lobes are controlled by the hypothalamus

Hypothalamus regulates functions of the

Pituitary gland and the adrenal gland

Oxytocin & Childbirth

• Stimulates uterine contractions and dilation of the cervix

• Released through a positive feedback mechanism throughout childbirth

  • OXT prompts uterine contractions and cervical stretching stimulates additional OXT synthesis which increases the contraction intensity and cervical dilation.

Oxytocin &

Lactation

• OXT is necessary for the milk ejection reflex (commonly referred to as “let-down”)

• In both males and females, OXT is thought to contribute to parent–newborn bonding, feelings of love and closeness, as well as in the sexual response.

Antidiuretic hormone (ADH)

• Osmoreceptors in the hypothalamus (sensitive to the concentration of blood) trigger ADH release when blood osmolarity increases.

  • Released by the posterior pituitary gland

• Functions in a negative feedback loop

• ADH (vasopressin) causes blood vessels to contract and increases blood pressure.

• Alcohol consumption inhibits the release of ADH => ↑ urination => dehydration

• Increase in ADH = higher water reabsorption during dehydration (When blood osmolarity increases, blood is too salty)

Diabetes insipidus is characterized by

Chronic dehydration.

• ADH levels are not high enough to trigger water reabsorption in the kidneys.

• Electrolyte imbalances can occur in severe cases of diabetes insipidus

Which type of stimuli causes ADH release?

Humoral stimuli (change in blood concentration)

Overlapping roles of OXT & ADH

• Given the structural similarity excess oxytocin, or synthetic oxytocin used in labor and delivery, can activate renal ADH receptors.

• Both oxytocin and ADH, acting as central neurotransmitters, are involved in pair bonding.

When a baby suckles at the breast, it triggers the release of oxytocin from the posterior lobe of the pituitary gland. Therefore, a ____ stimuli is responsible for the release of oxytocin.

Neural

FLAT PIG

F – Follicle stimulating hormone (FSH)

L – Luteinizing hormone (LH)

A – Adrenocorticotropic hormone (ACTH)

T – Thyroid stimulating hormone (TSH)

P – Prolactin (PRL)

i – (ignore)

G – Growth hormone (GH)

The anterior pituitary gland contains five main types of endocrine cells which secrete various hormones:

• Gonadotropes

• Corticotropes

• Thyrotropes

• Lactotropes

• Somatotropes

What do gonadotropes release

FSH and LH

What do corticotropes release

ACTH

What do thyrotropes release

TSH

What do lactotropes release

Prolactin

What do somatotropes release

Growth hormone

The hypothalamus produces a ___ to stimulate hormone production by other glands

• Releasing hormone (RH)

• Homeostatic control occurs by negative feedback

• (FLAT)

The hypothalamus produces both a

• Releasing hormone (PRH) and an inhibiting hormone (PIH)

PI

GH-RH release is

inhibited by GH-IH (somatostatin) release is stimulated by IGF-1 (somatomedin)

• Stimulates growth of skeletal muscle, cartilage, and many other tissues

G

Stunted growth could be due to an inhibition of ___

Somatomedin (IFG-1), GH-RH, or Somatostatin (GH-IH)

Follicle-stimulating hormone (FSH)

• Gonadotropin Releasing Hormone (GnRH) leads to increased release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

FSH stimulates male ___ and female ___.

Spermatogenesis, oocyte maturation

FSH production is inhibited by

Inhibin, a peptide hormone released by cells in the testes and ovaries

Luteinizing hormone (LH)

Stimulates testes to produce testosterone and ovaries to produce estrogen.

• These hormones lead to secondary sexual development in males and females, respectively.

• A surge in LH causes ovulation.

In males, _________ facilitates spermatogenesis while _______ facilitates testosterone synthesis.

FSH; LH

Gonadotropin-producing tumors can cause

Precocious (premature) puberty or hirsutism (facial hair in women).

Adrenocorticotropic hormone

• The corticotropin-releasing (CRH) hormone from the hypothalamus causes the corticotrophs to releas adrenocorticotropic hormone (ACTH) into capillaries

• ACTH travels through systemic circulation to stimulate the adrenal cortex

  • Zona fasciculata

  • Zone reticularis

Zona fasciculata

Produces cortisol – a stress-response hormone

Zona reticularis

Produces androgens

Glow- Zona glomerulosa

Salt (Mineral levels controled)

• Mineralocorticoids (primarily Aldosterone) – key hormone in the Renin, Angiotensin, Aldosterone System (RAAS)

Fast- Zona fasciculata

Sugar (Blood glucose)

• Glucocorticoids (cortisol, corticosterone, and cortisone) - crucial roles in various physiological processes (immunity, metabolism, stress, etc.)

Rex- Zona reticularis

Sex (Sexual properties)

• Androgens - contribute to the sex drive in women, development of pubic hair in boys and girls before puberty

Thyroid Stimulating hormone

• Thyrotropin-releasing hormone (TRH) leads to systemic thyroid stimulating hormone (TSH) secretion, increasing the synthesis and release of thyroid hormone to regulate metabolism.

• The hypothalamus senses body energy stores in part by receptors for the adipocyte hormone leptin.

• When reserves are low, the hypothalamus decreases metabolism by decreasing the thyroid hormone.

Prolactin (PRL)

• Prolactin helps to stimulate mammary gland development in females and stimulates milk production by the mammary glands

• Prolactin production is inhibited by the neurotransmitter dopamine (tyrosine derivative), also known as prolactin- inhibiting hormone (PIH).

• Prolactinomas cause galactorrhea and suppress gonadotropins, leading to decreased libido and infertility

Growth hormone

• Growth hormone-releasing hormone (GH-RH) leads to the release of growth hormone (GH), which stimulates tissue growth and metabolism.

• The liver releases somatomedins (IGF-1) in response to GH.

• somatomedins (IGF-1) activates somatostatin (GH- IH) and opposes GHRH.

Pituitary gigantism

Occurs in adolescents and children who have growth hormone excess before the fusion of their epiphyseal growth plates

Acromegaly

Occurs in adults who have growth hormone excess after the fusion of their epiphyseal growth plates

• Adults with acromegaly present with soft tissue overgrowth with the characteristic features of macrognathia, macroglossia, and enlarged hands and feet, hypertrophy of the knees, ankles, etc

Melanocyte-stimulating hormone (MSH)

• Pars intermedia secretes melanocyte-stimulating hormone (MSH)

  • Stimulates melanin production

• Virtually nonfunctional in adults except in

  • Pregnant women

  • Those with certain diseases. E.g Addison’s disease, Cushing's syndrome, etc.

Hypothalamic control of the anterior pituitary gland

Hormonal stimuli

Hypothalamic control of the posterior pituitary gland

Neural and humoral stimuli

Thyroid gland

• Butterfly-shaped organ, the thyroid gland is located anterior to the trachea

• The medial region, called the isthmus, is flanked by wing-shaped left and right lobes

• T4, T3, CT

Histological details of the thyroid gland

• The tissue of the thyroid gland is composed mostly of thyroid follicles.

• The colloid-filled follicles are the center of thyroid hormone production.

T3 is the more ___ form of thyroid hormone

Active

• T4 is converted to T3 when needed

Synthesis of Thyroid Hormones

1. Binding of TSH to its receptors in the follicle cells causes the transport iodide ions into the cytosol.

2. Iodide ions undergo oxidation to form iodine (I2)

3. In the colloid, enzymes link the iodine to the tyrosine amino acids in thyroglobulin to produce triiodothyronine (T3) or tetraiodothyronine, also known as thyroxine (T4).

4. T3 and T4 remain in the thyroid follicles until TSH stimulates endocytosis of colloid back into the follicle cells.

5. lysosomal enzymes break apart the thyroglobulin colloid, releasing free T3 and T4, which diffuse across the follicle cell membrane and enter the bloodstream.

6. T3 and T4 diffuse across the follicle cell membrane and enter the bloodstream.

7. 99% of the hormone is bound to proteins – released when levels drop

Low blood levels of T3 and T4 stimulate the release of

TRH

Metabolic role of Thyroid hormones

• T3 and T4 bind to intracellular receptors located on the mitochondria, they cause an increase in nutrient breakdown and the use of oxygen to produce ATP.

• T3 and T4 initiate the transcription of genes involved in glucose oxidation.

• abnormally increased level of heat is released as a byproduct of these reactions

• protein synthesis, and for fetal and childhood tissue development and growth

• first trimester is the critical period for fetal brain development – damage has irreversible consequences.

• increase the body’s sensitivity to catecholamines

Hyperthyroidism

• Autoimmune disease (antibodies against thyroid follicle cells mimic TSH actions and stimulate T3/T4 production)

• Symptoms include – exophthalmos, increased metabolic rate, sweating, & weight loss

Congenital iodine deficiency syndrome (cretinism)

Insufficient maternal intake of iodine (irreversible but preventable)

• Symptoms – Intellectual disability, short stature with disproportionately sized body, etc.

Prolactin (PRL) production and secretion by the anterior pituitary are tonically regulated by hypothalamic inputs. Which of the following neurotransmitters acts as the primary prolactin-inhibiting hormone (PIH)?

Dopamine

Thyroid hormones T 3 and T 4 play a critical role in controlling the body's basal metabolic rate. At the cellular level, how do they directly drive nutrient breakdown and ATP production?

By binding to intracellular receptors located on the mitochondria

Myxdema

• Inadequate iodine intake in adulthood

• Symptoms – Low metabolic rate, lethargy, mental sluggishness, feeling cold, goiter

• T3 + TH levels drop → TRH → TSH secreation

Parathyroid Glands

• Posterior to the thyroid

• regulate Ca2+ levels

Calcium homeostatis

Calcium homeostatsis High calcium

Low blood calcium

• neural and muscle super excitable

• muscle spasms

• higher RMP due to low Ca2+ levels, so Na+ voltage gated channels open eaiser

High blood calcium

• depressed neural and muscular function

• cardiac arrhythmias

A drop in phosphate levels would act as a

humoral stimuli (change in concentration)

To prevent abnormally high levels of phosphate,

phosphatonin (FGF23)

 inhibits phosphate reabsorption

 suppresses the production of Vit D

 suppresses PTH secretion

Adrenal glands

• The adrenal glands are wedges of glandular and neuroendocrine tissue adhering to the top of the kidneys by a fibrous capsule.

• Blood flows to each adrenal gland at the adrenal cortex and then drains into the adrenal medulla.