Ch 11+ 20 Endocrine Glands and Reproductive

How do endocrine glands communicate with the body vs. the nervous system?

• Nervous system: action potentials + neurotransmitters
  
  

• Endocrine: ductless glands secrete hormones into the bloodstream

What are neurohormones? Examples?

Neurotransmitters secreted into the blood by specialized neurons

• Epinephrine

• Norepinephrine

In general, what do hormones affect in their targets?

Their metabolism

What are amine hormones derived from? Examples?

Tyrosine or tryptophan

• Norepinephrine

• Epinephrine

• Thyroxine (thyroid)

• Melatonin (pineal)

What are polypeptide/protein hormones? Examples?

Longer chains of amino acids

• ADH

• GH

• Insulin

• Oxytocin

• Glucagon

• ACTH

• PTH

What are glycoproteins? Examples?

Peptide hormones with sugar attachments

• LH

• FSH

• TSH

What are steroids derived from? Examples?

Lipids (cholesterol)

• Testosterone

• Estrogen

• Progesterone

• Aldosterone

• Cortisol

Steroid vs. amino acid–based hormones: lipophilic or hydrophilic?

• Steroids: lipophilic (hydrophobic)
  
  

• Amino acid–based: hydrophilic (lipophobic), except thyroxine (lipophilic)

What’s the difference between NTs and hormones?

• Hormones are transported in blood

• Hormones have more diverse effects on targets

What must targets of both NTs and hormones have?

Specific receptor proteins for that chemical

Synergistic hormones: what are the 2 types?

1. Complementary: work together to produce one effect
   
   

2. Additive: produce a larger effect together than alone

Example of complementary synergism?

Nursing

• Prolactin → milk production

• Oxytocin → milk secretion

Example of additive synergism?

Epinephrine + norepinephrine → much stronger excitation together than alone

What is a permissive effect? Example?

One hormone enhances the target’s response to a 2nd hormone

• Estrogen ↑ progesterone receptors in the uterus → progesterone has a stronger effect

What are antagonistic hormones?

One hormone inhibits the effect of another

What is the physiological range?

The hormone concentration range in which targets produce a normal response

What is a pharmacological dose? Risk?

An administered hormone dose. If it falls outside the physiological range (too high or too low), it causes side effects, probably by binding receptors of closely related hormones

What is the priming effect (upregulation)?

Low hormone levels → the target adds more receptors → greater response (more sensitive)

What is desensitization (downregulation)?

Too much hormone, or exposure for too long → the target removes receptors → lesser response

What is pulsatile secretion? Purpose?

Hormone is released in pulses, so blood levels go up and down. This prevents overstimulation and downregulation (seen in most peptide hormones)

What 3 properties do hormone receptors have?

1. Specificity: bind only their own hormone

2. High affinity: bind strongly

3. Low capacity: a low hormone concentration activates them

Lipophilic hormones: where are their receptors, and what is their action?

• Receptors are in the cytoplasm/nucleus (the hormone diffuses through the membrane)

• Genomic action: activates genes → protein synthesis

• Slow: takes at least 30 min

Hydrophilic hormones: where are their receptors, and what is their action?

• Receptors are on the cell surface (the hormone can’t cross the membrane)

• Act through 2nd messengers → quick effects

• Nongenomic action: no gene expression

Why do lipid (steroid) hormones need carrier proteins?

They’re hydrophobic and plasma is about 90% water, so they’re carried through the blood and released from the carrier at the target to cross the membrane

Why are they called nuclear hormone receptors?

The receptor enters the nucleus and activates genes

Lipophilic vs. hydrophilic hormones: how do they act on the cell?

• Lipophilic (steroids): diffuse through the membrane → bind a receptor inside → turn on genes → new proteins (slow)
  
  

• Hydrophilic: bind a receptor on the cell surface → 2nd messenger (cAMP) → activates kinases → fast response

What do nuclear hormone receptors act as when bound to a hormone?

Transcription factors: they bind DNA and activate transcription

What 2 domains does a nuclear hormone receptor have?

1. Ligand (hormone)-binding domain: binds the hormone

2. DNA-binding domain: binds DNA

Where on the DNA does the receptor bind?

The hormone-response element (HRE), located next to the target gene

What is the HRE made of, and what’s needed before transcription can start?

• 2 half-sites

• 2 hormone-bound receptors must come together (dimerization) and each binds one half-site → transcription of the target gene

What does the thyroid secrete?

• Mostly T4 (thyroxine)

• Some T3 (triiodothyronine)

What carries T4 in the blood, and why is a carrier needed?

Thyroid-binding globulin (TBG). because T4 and T3 are lipophilic

Which thyroid hormone can enter cells?

What does protein-bound T4 do?

• Only free T4/T3 can enter cells

• Bound T4 serves as a reservoir

What happens to T4 inside the target cell, and where is its receptor?

• T4 is converted to T3

• T3 binds a receptor located in the nucleus (not the cytoplasm, unlike usual)

What does the thyroid receptor dimerize with?

One receptor binds T3 and the other binds retinoic acid. Each binds one half-site of the HRE → transcription

What is a heterodimer? Example?

2 different receptors dimerize

• T3 receptor + retinoic acid receptor

What is a homodimer? Example?

2 identical receptors dimerize

• Steroid hormone receptors

Steroid hormone pathway?

1. Steroid travels in blood attached to a carrier protein →

2. Steroid is released near the target cell →

3. Enters the cell through the membrane →

4. Binds to a receptor in the cytoplasm →

5. Hormone-receptor complex enters the nucleus →

6. 2 complexes join together (dimerize) →

7. Bind to specific DNA sites (HRE) →

8. DNA is transcribed into mRNA →

9. mRNA is translated into a protein →

10. Protein causes the target cell response

The remaining cards are hydrophilic hormone related. (Second messenger system)

What are the 3 advantages of 2nd messenger systems?

1. Amplify the signal

2. Need little ligand to activate

3. Lead to complex responses in the cell

In the cAMP system, what’s the 1st vs. 2nd messenger?

• 1st: the hormone (extracellular signal)

• 2nd: cAMP (carries the signal inside the cell)

What does adenylate cyclase do to ATP?

Removes 2 phosphates → cyclic AMP (cAMP)

cAMP 2nd messenger pathway?

1. Hormone binds to a receptor on the cell surface →

2. Activates a G protein →

3. G protein activates adenylate cyclase →

4. ATP becomes cAMP (2nd messenger) →

5. cAMP activates protein kinase →

6. Protein kinase adds phosphate groups to proteins →

7. Proteins activate or deactivate enzymes → cell response

In the Ca²⁺ 2nd messenger system, which enzyme does the G protein activate?

Phospholipase C (instead of adenylate cyclase)

What are the 2nd messengers made by phospholipase C? What do they do?

IP3(Inositol triphosphate) and DAG (diaglycerol), which cause Ca²⁺ release from the ER

What does released Ca²⁺ bind to?

Calmodulin → calcium-calmodulin → activates a protein kinase

Phospholipase C–Ca²⁺ pathway?

1. Hormone binds to a receptor on the cell surface →

2. Activates a G protein →

3. Activates phospholipase C →

4. Splits a membrane phospholipid into IP3 + DAG (2nd messengers) →

5. IP3 opens Ca²⁺ channels on the ER →

6. Ca²⁺ enters the cytoplasm →

7. Ca²⁺ binds to calmodulin →

8. Calcium-calmodulin activates protein kinase →

9. Protein kinase adds phosphate groups to enzymes → cell response

Epinephrine acts through which 2 receptors, and which 2nd messenger system does each use?

• Beta-adrenergic → cAMP system

• Alpha-adrenergic → phospholipase C–Ca²⁺ system

Epinephrine beta-adrenergic pathway (cAMP)?

1. Epinephrine binds the beta-adrenergic receptor

2. Activates a G protein → adenylate cyclase

3. ATP is converted to cAMP

4. cAMP activates protein kinase

5. Glycogenolysis: glycogen → glucose 1-phosphate → glucose 6-phosphate

6. Liver dephosphorylates it → free glucose → blood

Epinephrine alpha-adrenergic pathway (Ca²⁺)?

1. Epinephrine binds the alpha-adrenergic receptor

2. Activates a G protein → phospholipase C

3. Phospholipase C makes IP3

4. IP3 releases Ca²⁺ from the ER

5. Ca²⁺ binds calmodulin → activates protein kinase

6. Glycogenolysis → free glucose → blood

What’s the end result of both epinephrine pathways in the liver?

Protein kinase → glycogenolysis (glycogen breakdown) → glucose is released into the blood

What uses the tyrosine kinase 2nd messenger system?

Insulin and many growth factors

What is autophosphorylation?

After insulin binds, the 2 tyrosine kinase receptor units dimerize and each phosphorylates the other half → the receptor becomes active

Insulin (tyrosine kinase) pathway?

1. Insulin binds to tyrosine kinase receptors →

2. Receptors join together (dimerize) →

3. Receptors phosphorylate themselves (autophosphorylation) →

4. Activates a signaling cascade →

5. GLUT4 vesicles move to and insert into the cell membrane →

6. Glucose uptake increases →

7. Blood glucose decreases

Congrats you finished the first video’s flashcards

Main role of each endocrine organ?

• Gonads:

• Adrenal:

• Thyroid:

• Parathyroid:

• Pancreas:

• Gonads: produce gametes
  
  

• Adrenal: stress
  
  

• Thyroid: metabolism + calcium regulation

• Parathyroid: calcium regulation
  
  

• Pancreas: glucose regulation

Where is the pituitary, and what connects it to the hypothalamus?

It hangs below (inferior to) the hypothalamus, attached by the infundibulum (pituitary stalk)

What are the 2 lobes of the pituitary?

1. Anterior lobe (adenohypophysis)
   
   

2. Posterior lobe (neurohypophysis)

What does trophic mean for anterior pituitary hormones?

They have a nutritive effect on the target’s size

• High blood levels → target hypertrophies

• Low blood levels → target atrophies

What are the 6 anterior pituitary hormones and their targets?

1) Prolactin:

2) GH:

3) TSH:

4) ACTH:

5) FSH:

6) LH:

1. Prolactin → mammary glands (milk production)
   - No prolactin in males

2. GH → body organs (growth)

3. TSH → thyroid (thyroid releases T3/T4)

4. ACTH → adrenal cortex (stress)
   
   
   Gonadotropins:

5. FSH → gonads

6. LH → gonads

Effect of prolactin in males?

Impotence

What does “thyroid hormone” refer to?

T3 and T4 (thyroxine), which regulate metabolism

What does ACTH make the adrenal cortex secrete?

Cortisol and aldosterone (for stress)

FSH vs. LH function?

• FSH: gamete production (ovarian follicle growth, sperm production)
  
  

• LH: se* hormone production (estrogen in females, testosterone in males) + ovulation in females

How are ACTH and TSH regulated?

• ACTH: stimulated by CRH(Corticotropin-releasing hormone), inhibited by glucocorticoids
  
  

• TSH: stimulated by TRH(Thyrotropin-releasing hormone), inhibited by thyroid hormones

How is GH regulated?

• Stimulated by GHRH (growth hormone–releasing hormone)

• Inhibited by somatostatin

How are FSH and LH regulated?

• Both stimulated by GnRH (Gonadotropin-releasing hormone)

• Both inhibited by sex steroids

• FSH is also inhibited by inhibin

How is prolactin regulated?

Inhibited by PIH (prolactin-inhibiting hormone)

What controls the release of anterior pituitary hormones?

• Hypothalamic releasing factors (releasing hormones), which trigger release
  
  

• Hypothalamic inhibiting factors (inhibiting hormones), which prevent release
  
  

  • Feedback from target gland hormone levels

Which 3 hypothalamus → anterior pituitary pathways must you know entirely?

1. TSH (thyroid)

2. ACTH (adrenal cortex)

3. Gonadotropins: FSH + LH (gonads)

General hypothalamic control pathway?

Hypothalamus releases a releasing hormone (RH) → anterior pituitary releases its hormone → targets its organ → target releases its hormones → effect on the body

3 types of feedback in the hypothalamic-pituitary-gonad axis?

• Short feedback loop: the anterior pituitary inhibits the hypothalamus’s releasing hormone
  
  

• Negative feedback: target gland hormones inhibit the hypothalamus and the anterior pituitary
  
  

• Positive feedback: estrogen triggers the “LH surge” during the menstrual cycle

Gonadotropin pathway?

1. Hypothalamus releases GnRH →

2. Anterior pituitary releases FSH + LH →

3. FSH stimulates egg/sperm production →

4. LH stimulates estrogen/testosterone production →

5. Excess sex hormones cause negative feedback →

6. Hypothalamus decreases GnRH; anterior pituitary decreases responsiveness to GnRH →

7. FSH + LH decrease →
   
   Summary:
   Hypothalamus → GnRH → Anterior pituitary → FSH + LH → Gonads

Why does inhibiting the anterior pituitary stop FSH/LH even if GnRH is still released?

The anterior pituitary no longer responds to GnRH, so no FSH or LH is made or released

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1. Follicular phase (days 1–14): one follicle develops
   
   

2. Ovulation (day 14): the oocyte (egg) exits the ovary
   
   

3. Luteal phase (days 14–28): the remaining follicle cells become the corpus luteum

What does the corpus luteum secrete, and why?

Progesterone, to prepare for embryo implantation

What happens to the corpus luteum if the egg isn’t fertilized?

It degenerates into the corpus albicans → the cycle restarts

3 phases of the uterine cycle?

1. Menstrual (days 1–5): Uterine lining sheds →

2. Proliferative (days 6–14): Uterine lining rebuilds →

3. Secretory (days 15–28): Uterine lining releases nutrients to support a potential embryo

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1. FSH: Stimulates ovarian follicles to grow (blue arrow – days 1–14).
   
   

2. Estrogen: Growing follicles release estrogen, which rebuilds the uterine lining and lowers FSH (yellow arrow – days 6–14).
   
   

3. LH: A sudden LH surge triggers ovulation and formation of the corpus luteum (purple arrow – around day 14).
   
   

4. Progesterone: The corpus luteum releases progesterone, which maintains the uterine lining and prepares it for implantation (green arrow – days 15–28).

FELP mnemonic

• F = FSH → Follicle growth (releasing E)

• E = Estrogen → Endometrium rebuilds

• L = LH → Ovulation

• P = Progesterone → Prepares lining for implantation

What’s the purpose of the hormones in the ovarian/uterine cycles?

To synchronize events in the ovary with events in the uterus

What hormone switches the uterus from

menstrual → proliferative?

From proliferative → secretory?

From secretory → menstrual?

• Menstrual → proliferative: ↑ estrogen
  
  

• Proliferative → secretory: ↑ progesterone
  
  

• Secretory → menstrual: ↓ progesterone

What triggers ovulation?

The LH surge at day 14

Ovarian and uterine cycle hormone pathway?

• Days 1–14: FSH increases → follicle grows → estrogen increases → menstrual phase → proliferative phase

• Around Day 14: LH surges → ovulation → remaining follicle becomes the corpus luteum
  
  

• Days 14–28: Corpus luteum → progesterone increases → secretory phase (uterus prepares for implantation)

  • No fertilization: Corpus luteum becomes corpus albicans → estrogen and progesterone decrease → menstruation begins → cycle restarts

What does ADH (vasopressin) do?

Targets the kidneys → water conservation (we pee less), released when dehydrated

What does oxytocin do?

• Uterine contractions during birth (parturition)

• Mammary alveoli contraction → milk ejection

Where are ADH and oxytocin made?

• ADH: supraoptic nuclei of the hypothalamus
  
  

• Oxytocin: paraventricular nuclei of the hypothalamus

How do posterior pituitary hormones get there?

Made by hypothalamic neurons → travel down the axons (hypothalamo-hypophyseal tract) → stored in axon terminals in the posterior pituitary → released

Anterior vs. posterior pituitary: which makes its own hormones?

• Anterior: makes and releases its own hormones (when triggered by hypothalamic RH)
  
  

• Posterior: only stores and releases hormones made by the hypothalamus

Where are the adrenal glands, and what are their 2 parts?

On top of the kidneys

• Outer: adrenal cortex

• Inner: adrenal medulla

What does the adrenal medulla secrete, and what controls it?

Mostly epinephrine, controlled by the sympathetic NS.

Adrenal medulla vs. cortex: which type of stress?

• Medulla: short-term/immediate stress (fight or flight)
  
  

• Cortex: longer-term stress

What does the adrenal cortex secrete, and what controls it?

Controlled by ACTH

• Cortisol

• Aldosterone

• Some sex steroids

How does cortisol help with stress?

• Switches the body from glucose to lipid use (except the nervous system, which keeps using glucose)

• Stimulates gluconeogenesis

What does aldosterone do?

Kidneys reabsorb Na⁺ (and water) and secrete K⁺ → water conservation

What is general adaptation syndrome (GAS)?

The nonspecific response to long-term stress, which causes ACTH and cortisol release

ACTH (stress) pathway?

1. Long-term stress → hypothalamus releases CRH →
   
   

2. CRH stimulates anterior pituitary to release ACTH →
   
   

3. ACTH stimulates adrenal cortex to release cortisol →
   
   

4. Increased cortisol causes negative feedback → hypothalamus decreases CRH and anterior pituitary decreases ACTH

4 negative effects of chronic stress (high cortisol)?

1. Atrophy of the hippocampus → memory loss

2. Reduced sensitivity to insulin (insulin resistance)

3. Inhibition of vagus nerve activity

4. Suppression of GH, thyroid hormone and gonadotropins

How does chronic stress lead to insulin resistance?

Cortisol switches the body to lipid use → ↑ blood glucose → ↑ insulin → insulin receptors (tyrosine kinase) downregulate → ↓ insulin sensitivity → can lead to diabetes

Effects of epinephrine/norepinephrine during “fight or flight”?

• ↑ Respiratory rate

• ↑ HR and cardiac output

• General vasoconstriction → ↑ venous return and BP

• Glycogenolysis + lipolysis → more fuel for ATP

What 2 hormones does the thyroid release, and what does each regulate?

• Thyroxine (T3 + T4) → metabolism

• Calcitonin → Ca²⁺

What is basal metabolic rate (BMR)?

How fast the body metabolizes (the sum of all anabolic + catabolic reactions), set by T3/T4