NS 3410: Endocrine System

crino

to secrete

exocrine

- A gland that secretes a substance out through a duct (multicellular) onto an epithelial surface
- include the salivary glands, sweat glands and glands within the gastrointestinal tract
- apocrine, holocrine, merocrine

endocrine

- A ductless gland that secretes a substance (a hormone) for export into bloodstream
- autocrine, intracrine, paracine

apocrine glands

* portion of the plasma membrane buds off the cell in a membrane bound vesicle
* Example is lipid secretion from mammary gland

merocrine glands

- products are contained in vesicles and are secreted by exocytosis
- No part of the gland is damaged or lost
- Example is sweat gland
- Least destructive to gland

holocrine glands

- cell ruptures to release contents
- Example is sebaceous glands of skin
- Most disruptive to gland

hormone

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"

amines

- amino acid derivatives
- examples: epinephrine/dopamine
- Secreted by exocytosis
- Dissolve in plasma (water soluble / polar)
- Short half-life
- Receptor found on cell membrane
- Response rapid

peptides

- short chains of amino acids; proteins
- examples: TSH, LH, FSH
- Secreted by exocytosis
- Dissolve in plasma (water-soluble / polar)
- Short half-life
- Receptor found on cell membrane
- Response rapid

thyroid hormone

- an amine
- Modified so that excreted as lipid
- Does not dissolve (hydrophobic) and binds to a carrier protein
- Longer half-life
- Active hormone is T3 (triiodothyronine) and its precursor T4 (thyroxine)
- Assumed taken up into cells primarily by passive diffusion
- T3/T4 are amino acid derivatives and we know amino acids need membrane carrier proteins
- they get into cells by carrier mediated transmembrane transport

steroids

- cholesterol derivatives
- examples: estrogen, testosterone, vitamin D
- Secreted by simple diffusion
- Do not dissolve in plasma - need a transport protein
- Longer half-life
- Traditionally assumed gets into cell by diffusion
- Receptor found within cell cytoplasm, nucleus, or on cell membrane
- Response takes longer (synthesize proteins) [can have rapid effects]

paracine hormone

* has local effects on cells other than those in which they were produced.
* Produced within one tissue and regulate a different tissue of the same organ
* example: sex steroids

autocrine hormone

- The hormone acts on the same cell type in which it was produced
- Example: Insulin - pancreatic islet B cells

intracrine hormone

- The hormone acts within the specific cell without ever being released

Non-genomic effects

- primary target is the cell membrane
- Activation/repression of pre-existing cell proteins
- Set off intracellular second messengers
- Rapid onset of action
- Proteins and amine hormones
- Steroid hormones can also cause non-genomic effects mediated by cell membrane bound receptors

Genomic effects

- primary action through specific intracellular receptors and HRE on target gene
- Gene expression and new protein synthesis
- long latency of onset
- Steroid hormones and thyroid hormone

hormone binding protein

- plasma proteins that bind hormone and transport throughout body
- thyroid and steroid hormones need these

hormone receptor

- Found in target tissues.
Cell must express this in order to be responsive to the hormone
- Can be expressed on the cell membrane or within the cell

hormone response element

- genes that are responsive to a hormone will express this to recognize the hormone-receptor complex and can then increase or decrease expression of the target gene
- Vitamin D (VDRE)
- Estrogen (ERE)

humoral stimuli

- secretion of hormones in direct response to changing blood levels of ions and nutrients
- Ex: concentration of calcium ions in the blood
• Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone)
• PTH causes Ca2+ concentrations to rise and the stimulus is removed

Chief (principal) cells

secrete parathyroid hormone

CaSR

- Calcium sensing receptors- in the Parathyroid gland; G-protein coupled receptors
- increases PTH when serum Ca level drops

Parafollicular cells (C cells)

- cells in the thyroid gland which produce calcitonin when serum Ca levels are elevated

parathyroid hormone

A hormone secreted by chief cells in the parathyroid gland which increases blood Ca levels
Effects:
• Kidney to increase Ca reabsorption - decrease urinary Ca loss
• Kidney to increase enzyme that makes active form of vitamin D (1,25(OH)2D or 1,25-dihydroxyvitamin D)
• Bone to stimulate Ca loss from bone (resorption)

1,25-dihydroxyvitamin D

- A hormone secreted by the kidney that increases Ca levels in blood
- also called calcitriol
Effects:
• Intestine to increase Ca absorption from diet
• Bone to stimulate Ca loss from bone (resorption)

Hormonal stimuli

- release of hormones in response to hormones produced by other endocrine organs

adeno

means gland

vitamin D Binding Protein (DBP)

- primary role is to isolate vitamin D sterols in the serum
- Prolongs half-life
- Provides circulating store of 25(OH)D for periods of D insufficiency
- Minimizes urinary losses
- Slows entry of D into metabolic breakdown pathways

megalin

endocytic receptor located on the kidney which helps the resorption of DBP-25(OH)D3 into the proximal tubules

7-dehydrocholesterol

A precursor cholesterol compound in the skin that when irradiated by sunlight produces (D3).

25-hydroxylase

an enzyme which converts inactive vitamin D2 and D3 into 25(OH)D - calcidiol

CYP2R1

gene which encodes for the enzyme 25-hydroxylase

1-alpha-hydroxylase

enzyme that converts 25-hydroxy vitamin D to 1,25-dihydroxy vitamin D, the biologically active form of the molecule.

CYP27B1

gene which encodes for the enzyme 1-alpha hydroxylase

25(OH)D

- the precursor to 1,25(OH)2D
- made in the liver
- also called calcidiol

24-hydroxylase

enzyme which converts 25(OH)D into 24,25(OH)2D in the kidney when no more calcitriol is needed

CYP24A1

gene which encodes for 24-hydroxylase

Rickets

- a disease of impaired bone mineralization in children
- If circulating Ca and P concentrations are not maintained at super-saturated concentrations, defective bone mineralization will ensue
- Causes:
1. Calcium / Vitamin D Deficiency
2. Genetic disorders of Ca / D / or phosphorus metabolism

Vitamin D dependent rickets Type 1B

- very rare VDDR
- person lacks 25-hydroxylase
- low levels of 25(OH)D and 1,25(OH)2D

Vitamin D dependent rickets Type 1A

- rare form of VDDR
- person lacks 1-alpha-hydroxylase
- low levels of 1,25(OH)2D but normal levels of 25(OH)D
- also called pseudovitamin D deficiency rickets

Vitamin D dependent rickets Type 2A

- hereditary VDDR
- 1,25(OH)2D hormone is made but individuals are resistant to hormone action
- VDR gene is mutated

Vitamin D-dependent rickets Type 2B

- hereditary VDDR
- 1,25(OH)2D hormone is made but there are problems with the hormone receptor elements
- normal levels of 25(OH)D and low to normal levels of 1,25(OH)2D

alopecia

lack of hair

anterior pituitary

- glandular tissue (75% of the weight)
- shares direct, vascular connection with the hypothalamus
- synthesizes and releases hormones

posterior pituitary

- neural tissue - neurosecretory cells (25% of the weight)
- shares neural connection with the hypothalamus - extension of the hypothalamus
- stores and releases two neurohormones

pituitary gland

- endocrine gland inferior to the hypothalamus
- connected to the hypothalamus via the infundibulum

hypophyseal portal system

- a blood vessel system that directly connects the hypothalamus with the anterior pituitary
- contains:
• Superior hypophyseal artery
• Capillary bed
• Portal vessels
• Capillary bed
• Hypophyseal veins

somatotrophs

secrete growth hormone (GH)

lactotrophs

secrete prolactin (PRL)

thyrotrophs

secrete thyroid stimulating hormone (TSH)

corticotrophs

secrete adrenocorticotropic hormone (ACTH)

gonadotrophs

secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

Thyroid Stimulating Hormone (TSH)

- target: thyroid gland
- effect: secretion of thyroid hormones
- regulatory hormone: thyrotropin-releasing hormone (TRH)

Adrenocorticotropic hormone (ACTH)

- target: adrenal cortex (zona fasiculata)
- effect: secretion of glucocorticoids
- regulatory hormone: corticotropin-releasing hormone

Follicle-stimulating hormone (FSH)

- target: follicle cells of ovaries; nurse cells of testes
- effect: secretion of estrogen, stimulates sperm maturation
- regulatory hormone: gonadotropin-releasing hormone (GnRH)

Lutenizing hormone (LH)

- target: follicle cells of ovaries; endocrine cells of testes
- effect: ovulation, secretion of testosterone
- regulatory hormone: gonadotropin-releasing hormone (GnRH)

Prolactin (PRL)

- target: mammary glands
- effect: production of milk
- regulatory hormone: prolactin-releasing factor (PRF) & prolactin-inhibiting hormone (PIH)

Growth hormone (GH)

- target: all cells
- effect: protein synthesis, growth, lipid mobilization and catabolism
- regulatory hormone: GH-inhibiting and releasing hormone (GH-IH) (GH-RH)

Erythropoietin (EPO)

- a peptide hormone, produced naturally by the kidneys and released into circulation
- binds to EPO-R on cell membranes in the bone marrow to stimulate RBC production
- target tissues: lymph vessel, tumor cells, blood vessel, bone marrow

cortisone

- decreases inflammation \= faster recovery
- Steroid hormone
- Non-genomic - binds to Glucocorticoid Receptors (GR) on membranes that lead to multiple intracellular signaling cascades

disorders of sexual development (DSD)

- A general term used for a variety of conditions in which a person is born with a reproductive or sexual anatomy that doesn't seem to fit the typical binary definition of female or male
- ex. hyperandrogenism \= excess androgen

anti-mullerian hormone

- a peptide hormone secreted by Sertoli cells of the testis that prevents the development of the female internal reproductive tract
- non-genomic effects

sex-determining region Y (SRY)

- a gene on the Y chromosome that specifies male development
- product is Testis determining factor

Testis Determining Factor (TDF)

protein encoded by a gene in the SRY that triggers testes formation

5-alpha reductase

an enzyme that converts testosterone into dihydrotestosterone

5 alpha reductase deficiency

- affects males
- inability to convert testosterone to DHT
- female external genitalia and male internal genitalia

Dihydrotestosterone (DHT)

- The 5-alpha-reduced metabolite of testosterone
- a potent androgen that is principally responsible for the masculinization of the external genitalia in mammals.

Congenital adrenal hyperplasia

~50% of DSD cases
• Adrenal glands produce too much testosterone, which can influence sexual development in females
• Hyper "active" and plasia "formation, growth"
• Abnormally enlarged adrenal glands

Androgen insensitivity syndrome (AIS)

- A syndrome caused by a mutation of the androgen receptor gene that renders tissues insensitive to androgen.
- Affected XY individuals are phenotypic females, but they have internal male genitalia

Complete AIS

• Appears female at birth with female external genitalia
• still has internal male genitalia

Partial AIS

• Ambiguous genitalia at birth

testosterone

- an anabolic steroid hormone
- released from the testes and ovaries
- Circulates in bloodstream bound to one of two types of transport proteins:
•Sex hormone binding protein (SHBP) ~70%
•Albumin ~30%

Zona reticularis

- a zone of the adrenal cortex
- secretes androgens like testosterone
- Androgen secretion is stimulated by ACTH

Hyperandrogenism

- higher than normal androgens (testosterone)
- symptoms: hidradenitis suppurativa (inflamed swollen lumps on skin), alopecia (hair loss on the head), hirsutism (male pattern hair growth), acne and masculine appearance.

vitamin D a steroid hormone (T/F)

true

the sun provides which type of vitamin D

D3

diet provides which type of vitamin D

D2 and D3

rickets is caused by

vitamin D deficiency

calcium requires ____ for adequate absorption and utilization

calcitriol (active vitamin D)

effect of PTH and Vitamin D on calcium levels

Increases calcium

effect of calcitonin on calcium levels

decreases calcium

inactive D2 and D3 are converted into _______ by the liver via the enzyme 25-hydroxylase259OH

25(OH)D -→ prohormone

what happens when UV rays from the sun hit our skin

7-dehydrocholesterol is converted to cholecalciferol (vitamin D3)

D3 is found in

sun, and fish

D2 is found in

diet (mushrooms)

another name for vitamin D2

ergocalciferol

the vitamin D2 and D3 from the sun and diet are not used by the body immediately because

they are not active yet (need to go through a series of reactions first)

the active form of vitamin D is called

1,25 dihydroxy vitamin D (calcitriol)

inactive vitamin D3 or D2 absorbed by the body will first bind to DBP (D binding protein) and then taken to the

Liver

what happens to inactive vitamin D in the liver

25 hydroxylase in the liver converts the inactive vitamin D to 25 OH Vitamin D (calcidiol)

25 OH Vitamin D (calcidiol) produced in the liver then goes to the

kidneys

what happens to calcidiol in the kidneys

it becomes 1,25 dihydroxy vitamin D (calcitriol)

\
CONGRATS, you’ve made the active form

The conversion of calcidiol to calcitriol is regulated by

PTH

25(OH)D is converted into 1,25 (OH2)D (calcitriol) through teh kidneys via the enzyme

1-alpha-hydroxylase

RANKL is expressed on

osteoblasts

RANK is expressed on

preosteoclast

vitamin D has a ______ feedback regulation

negative

High level of ________ decreases

its synthesis and PTH synthesis

1,25(OH)2D -→ negative feedback

cytochrome # for 25-hydroxylase

CYP2R1 (liver)

cytochrome # for 1-alpha-hydroxylase

CYP27B1 (kidney) to form 25-(OH)2D