NS 3410: Endocrine System

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122 Terms

1

crino

to secrete

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2

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

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endocrine

  • A ductless gland that secretes a substance (a hormone) for export into bloodstream

  • autocrine, intracrine, paracine

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4

apocrine glands

  • portion of the plasma membrane buds off the cell in a membrane bound vesicle

  • Example is lipid secretion from mammary gland

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5

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

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6

holocrine glands

  • cell ruptures to release contents

  • Example is sebaceous glands of skin

  • Most disruptive to gland

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7

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"

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8

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

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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

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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

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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]

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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

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autocrine hormone

  • The hormone acts on the same cell type in which it was produced

  • Example: Insulin - pancreatic islet B cells

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14

intracrine hormone

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

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15

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

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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

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hormone binding protein

  • plasma proteins that bind hormone and transport throughout body

  • thyroid and steroid hormones need these

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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

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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)

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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

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Chief (principal) cells

secrete parathyroid hormone

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22

CaSR

  • Calcium sensing receptors- in the Parathyroid gland; G-protein coupled receptors

  • increases PTH when serum Ca level drops

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Parafollicular cells (C cells)

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

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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)

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25

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)

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Hormonal stimuli

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

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adeno

means gland

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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

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megalin

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

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7-dehydrocholesterol

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

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25-hydroxylase

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

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CYP2R1

gene which encodes for the enzyme 25-hydroxylase

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1-alpha-hydroxylase

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

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CYP27B1

gene which encodes for the enzyme 1-alpha hydroxylase

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25(OH)D

  • the precursor to 1,25(OH)2D

  • made in the liver

  • also called calcidiol

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24-hydroxylase

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

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CYP24A1

gene which encodes for 24-hydroxylase

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38

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

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Vitamin D dependent rickets Type 1B

  • very rare VDDR

  • person lacks 25-hydroxylase

  • low levels of 25(OH)D and 1,25(OH)2D

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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

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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

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42

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

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43

alopecia

lack of hair

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44

anterior pituitary

  • glandular tissue (75% of the weight)

  • shares direct, vascular connection with the hypothalamus

  • synthesizes and releases hormones

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45

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

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46

pituitary gland

  • endocrine gland inferior to the hypothalamus

  • connected to the hypothalamus via the infundibulum

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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

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48

somatotrophs

secrete growth hormone (GH)

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49

lactotrophs

secrete prolactin (PRL)

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50

thyrotrophs

secrete thyroid stimulating hormone (TSH)

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51

corticotrophs

secrete adrenocorticotropic hormone (ACTH)

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52

gonadotrophs

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

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53

Thyroid Stimulating Hormone (TSH)

  • target: thyroid gland

  • effect: secretion of thyroid hormones

  • regulatory hormone: thyrotropin-releasing hormone (TRH)

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54

Adrenocorticotropic hormone (ACTH)

  • target: adrenal cortex (zona fasiculata)

  • effect: secretion of glucocorticoids

  • regulatory hormone: corticotropin-releasing hormone

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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)

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Lutenizing hormone (LH)

  • target: follicle cells of ovaries; endocrine cells of testes

  • effect: ovulation, secretion of testosterone

  • regulatory hormone: gonadotropin-releasing hormone (GnRH)

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Prolactin (PRL)

  • target: mammary glands

  • effect: production of milk

  • regulatory hormone: prolactin-releasing factor (PRF) & prolactin-inhibiting hormone (PIH)

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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)

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59

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

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60

cortisone

  • decreases inflammation = faster recovery

  • Steroid hormone

  • Non-genomic - binds to Glucocorticoid Receptors (GR) on membranes that lead to multiple intracellular signaling cascades

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61

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

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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

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sex-determining region Y (SRY)

  • a gene on the Y chromosome that specifies male development

  • product is Testis determining factor

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Testis Determining Factor (TDF)

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

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5-alpha reductase

an enzyme that converts testosterone into dihydrotestosterone

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5 alpha reductase deficiency

  • affects males

  • inability to convert testosterone to DHT

  • female external genitalia and male internal genitalia

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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.

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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

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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

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Complete AIS

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

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Partial AIS

• Ambiguous genitalia at birth

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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%

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Zona reticularis

  • a zone of the adrenal cortex

  • secretes androgens like testosterone

  • Androgen secretion is stimulated by ACTH

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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.

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75

vitamin D a steroid hormone (T/F)

true

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76

the sun provides which type of vitamin D

D3

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77

diet provides which type of vitamin D

D2 and D3

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78

rickets is caused by

vitamin D deficiency

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79

calcium requires ____ for adequate absorption and utilization

calcitriol (active vitamin D)

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80

effect of PTH and Vitamin D on calcium levels

Increases calcium

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81

effect of calcitonin on calcium levels

decreases calcium

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82

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

25(OH)D -→ prohormone

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83

what happens when UV rays from the sun hit our skin

7-dehydrocholesterol is converted to cholecalciferol (vitamin D3)

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84

D3 is found in

sun, and fish

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85

D2 is found in

diet (mushrooms)

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86

another name for vitamin D2

ergocalciferol

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87

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)

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88

the active form of vitamin D is called

1,25 dihydroxy vitamin D (calcitriol)

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

Liver

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90

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)

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

kidneys

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92

what happens to calcidiol in the kidneys

it becomes 1,25 dihydroxy vitamin D (calcitriol)

CONGRATS, you’ve made the active form

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93

The conversion of calcidiol to calcitriol is regulated by

PTH

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94

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

1-alpha-hydroxylase

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95

RANKL is expressed on

osteoblasts

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96

RANK is expressed on

preosteoclast

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97

vitamin D has a ______ feedback regulation

negative

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98

High level of ________ decreases

its synthesis and PTH synthesis

1,25(OH)2D -→ negative feedback

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99

cytochrome # for 25-hydroxylase

CYP2R1 (liver)

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cytochrome # for 1-alpha-hydroxylase

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

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