steroids

What are steroids 

• a four ring carbon structure 

• a large class of organic compunds 

Properties of steroid hormones

• lipohilic can cross membrane

• persist in tissue fluid

• low-molecular weight

Class of steroids 

• Glucocorticoids 

• mineralocorticoids 

• sex steroids

John Hunter 

• testis transplantations from roosters to hens 

Arnold Berthold

• removed testicles from birds and moved to abdomen 

Brown-sequard

• injected testicular extracts to rejuvenate mental and physical ability 

Adolf Butenandt 

• isolated estrogen and estriol

• synthesized androsterone and progesterone

• Chem nobel prize

Carl Djerassi

• characterized this class of molecules 

• Father of the pill

How are all steroids produced

• Cholesterol

• then converted to pregenolone (rate limiting)

Name of the skeleton structure of all steroids

cyclopentanoperhydrophenanthrene

Important class of enzymes in production and termination

cytochrome P450

what are the sex steroids

• Estrone 

• Estriol

• Estradiol 

• Testosterone 

• Dihydrotestosterone 

Enzymes used in the production of sex steroids

• Aromatase for all the estrogens 

• 5a-reductase for dihydrgentestosterone 

Where are sex steroids synthesized

• peripheral tissue 

Where are mineralcorticoids and glucocorticoids made

adrenal cortex

Where in the cell are steroids made

• mitochondria 

How can cholesterol be synthesized

• from acetate in the endoplasmic reticulum 

• de novo synthesis 

How are sterioids released

• into blood 

• bound to carrier proteins in circulation 

Steroid receptor types 

Nucler 

• class 1 (needs HSP)

• class 2 (straight to nucleus)

What is the main response of steroids

• transcriptional regulation 

What molecules use class 1 nuclear receptors

• androgen

• estrogen 

• glucocorticoids 

• progestrone 

what molecules use class 2 receptors

• non-steroid hormones

• retinoic acid 

• retinoid x receptors 

• thyroid hormone receptors 

How is transcription rate regulated

• receptors can be kept in a inactive state by inhibitory proteins

What do corticoids and glucocorticoids need to form to bind to a receptor

• a dimer

How are steroids terminated

• enzymatically catabolized in the liver and kidneys

• Cytochrome P450 

What is difference spectroscopy 

• where you place a base line and a sample through a spectrometer to see what wavelength of light is absorbed 

• CYP absrob 450nm 

what do CYPs do

• allow toxic chemicals to be degraded and removed from the body

• A very samll number of these can metbolize 90% of all drugs 

• can also activate some compunds 

• codeine to morphine 

what can inhibit CYPs

• grapefruit 

• can cause accidental overdose 

What is the main mineralocorticoid 

Aldosterone 

Receptros fro Mineralocorticoids

• type of glucocorticoids 

• intercellular 

• Type 1 ytosolic 

How is aldosterone produced

• produced in response to a protein called angiotensin 

• released when blood flow to kidney drops

Main Glucocorticoid

• cortisol

• stress hormone

Glucocorticoid receptors

• type 1 cytosolic receptors 

What is the endocrine response to stress 

• affects the HPA axis 

• Hypothalamus sends signal to pituitary (CRH)

• pituitary sends signals to adrenals (ACTH)

• adrenal cortex make cortisol 

How are isomers crested in glucocorticoid receptors 

• alternative splicing

• alternative translation initiation

Polymorphisms

• many forms of a receptor 

• some benefit some are harmful

What happens when something is wrong in crorisol levels

• Cushings (too much)

• Addison’s (too little)

What happens when there is somethng wrong with reception of cortisol

• Glucocorticoid resistance syndrome 

• impaired receptors 

Sex hormone receptors

• estrogen receptors

• androgen receptors 

• progesterone receptors 

Female sex sterioid diseases

• polycystic ovarian syndrome 

• Hirsutism 

• Menopause 

• Amenorrhea 

Male sex steroid disorders

• Hypogonadism 

• Androgen insensitivity 

• Gynecomastia 

• Kleinfelter’s syndrome