Endocrine #2 Flashcards
Osteoblasts
Bone generating cells
Osteocytes
Mature bone cells
Spider shaped
Maintain bone tissue
Osteoclasts
Bone destroying cells
Bone formation
The process by which osteoblasts synthesize bone
Osteoblasts function in groups of connected cells
Osteons
Group of organized osteoblasts together that make bone
Individual osteoblasts cannot synthesize bone by themselves
Bone resorption
The process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood
Bone homeostasis
The balance between bone formation and bone resorption
If the body is low on Ca, what occurs?
Parathyroid hormone (PTH) will be released and
1) bone resorption will increase
2) Ca elimination by the kidney will decrease
3) Ca absorption increases in the gut
Parathyroid hormone
88 aa protein, only the first 34 are required for activity
T1/2 in plasma ~4 minutes
What are the parathyroid receptors?
PTHR1
PTHR2
PTHR1
Located in bone and kidneys
Activation leads to expression of RANK ligand (RANKL) - leading to bingin and activation of osteoclasts and bone resorption
PTHR2
Located in CNS, pancreas, testis, placenta
What effects does PTH have on the kidney?
Maximize Ca resorption
Decrease PO4 resorption
Enhance vitamin D production
PTH effect on vitamin D
PTH enhances the production of calcitrol (active form of vitamin D)
This enhances the absorption of Ca from the gut
Calcitrol
Plays a complex role in the Ca homeostasis
- Increases Ca absorption in the gut (main one)
- decrease Ca excretion in kidney
- increase bone resorption and mineralization
- increase osteoclasts development
- decrease PTH secretion
T/F - Vitamin D is only related to Calcium
False - Most cells have vitamin D receptors
There are hundreds of vitamin D responsive genes
Calcitonin
Released by parafollicular cells of the thyroid in response to high serum Ca concentrations
Counteracts the effect of PTH
What are the effects of Calcitonin
Increases bone formation
Decreased kidney resorption of Ca
Decreases Ca absorption by the gut
Bisphosphonates
A class of drugs that prevent the loss of bone mass
Used to treat osteoporosis and similar diseases
Most commonly prescribed drugs to treat osteoporosis
Bisphosphate effects
Inhibit bone resorption and osteoclast activity
Restore bone density
Mechanism is not totally understood
Where do androgens (Testosterone) come from?
95% come form Leydig cells of the tests (some come from ovary)
5% from the adrenal gland
What stimulates testosterone synthesis and release?
LH
Theraputic use of Androgen
Androgen deficiency (low T, etc)
What are the major types of Estrogen?
Estradiol (E2)
Estrone (E1)
Estriol (E3)
Estradiol (E2)
Major secretory product of ovary
Estrone (E1) and Estriol (E3)
Made in liver from estradiol
Natrual estrogens
From which synthetic estrogens were derived (estradiol, estrone, estriol)
Synthetic estrogens
Most commonly used in oral contraceptives
Synthetic nonsteroidal compounds with estrogenic activity
Have also been used clinically
What are the major clinical uses of Estrogen?
Primary hypogonadism
Postmenopausal hormonal therapy
Other uses
How is estrogen used to help treat hypogonadism
For replacement therapy in estrogen-deficiencies due to underdeveloped ovaries, premature menopause, castration, or menopause
Attempts to mimic physiology of puberty
How is estrogen used to help treat postmenopausal hormonal therapy
Prevent hot flashes and osteoporosis
Use only the lowest possible doses because of increased risks for breast and endometrial cancer
Estrogen receptor and treatment of breast cancer
If the breast cancer cells are estrogen receptor positive, estrogen is likely to be driving cell proliferation
The drug tamoxifen antagonizes the effect of estrogens in breast cancer cells and blocks proliferation
Class 1 Nuclear Receptor Molecular Biology
1) Binding of agonists (eg estradiol to estrogen receptor) produces a conformational change that exposes AF-2 region of the receptor
2) Co-activator proteins such as SRC-1 can only bind to the receptor if AF-2 is exposed. Thus, the co-activators only bind to the receptor if agonist is bound
3) Antagonists bind perfectly well to the receptor, but their binding does not lead to exposure of AT-2. Therefore, the antagonist receptor binds to the DNA, but does not bind co-activators, and the antagonist does not activate transcription
Tamoxifen
It’s a SERM (selective estrogen receptor modultor)
Acts as an antagonist in some tissues but acts as an agonist in other tissues
It is speculated that things like availability of co-activators determines if it acts as an agonist or antagonist
Where are progestins synthesized?
Corpus luteum
Placenta
Adrenal cortex
Progestins are the precursors to what?
Androgens
Estrogens
Adrenocortical hormones
Progestins play a biological role in what?
Menstrual cycle and pregnancy
side note: males have progesterone receptors too, but it’s not tremendously understood what effects they have on male sexuality
What is required during menstrual cycle for follicle development, ovulation, and pregnancy?
Coordinated pattern of FSH and LH secretion
What are the clinical uses of Progesterone?
Hormonal replacement therapy Contraception Diagnosis: estrogen secretion Dysmenorrhea Endometriosis
What effect do Estrogen + Progesterone oral contraceptives have?
Block LH and FSH release from the pituitary
What effect do Progesterone oral contraceptives have?
Thickening of cervical mucus (blocks sperm from contacting egg)
Block release of eggs from the ovary
What are the types of emergency oral contraceptive pills?
1) Higher doses of progesterone alone, or progesterone plus estrogen
2) RU486 (mifepristone) - a low efficacy progesterone partial antagonist
- lower dose: emergency oral contraceptive
- higher dose: abortifacient (first several months)
