Androgens

What are the 6 facts about androgens?

• Androgens are group names not single molecules

• Synthesis of androgens and related steroid hormones are made from cholesterol

• androgens have actions on multiple areas of the body including bone, muscle ,skin ,liver ,kidney, brain, immune system, bone marrow, and genital organs

• Testosterone is the primary & most well known androgen

• testosterone while active, is converted to more active form dihydrotestosterone

• testosterone is made in testes(men) & ovaries(women) in adrenals (both genders)

Explain the steps in the synthesis of androgens

What is the 5 role of androgens in both genders?

helps with:

• bone density

• muscle development

• puberty

• red blood cell production

• sexual desires & function

4 roles of androgens in women

• regulate menstruation

• aids conception & pregnancy

• minimizes bone loss (osteoporosis)

• stimulates pubic & underarm hair growth

3 roles of androgens in men

• deep voice

• hair growth on the face, scalp chest, underarm, genitals

• sperm development

explain the steps & identify the hormones in androgen synthesis in the male reproduction system

• LH stimulates testicular leydig cells to increase the synthesis of testosterone, which then diffuses into Sertoli cells

• In the sertoli cells, FSH stimulation increases ABP, which is important for maintaining high testicular concentration of testosterone necessary for spermatogenesis

Testosterone has what 2 types of effects

• androgenic effect

• anabolic effects

explain androgenic effects

• pertaining to the development of male characteristics

• differentiation & growth of male reproductive organs

• control of male sexual behavior, and the development & maintenance of male secondary characteristics that involve muscle, bone, larynx, hair

explain anabolic effects

Nitrogen retention by increasing the rate of protein synthesis & muscle mass while decreasing the rate of protein catabolism

MOA & regional effects of testosterone &DHT

• Nuclear receptor located throughout the body. Testosterone & DHT have activity at these receptors

• Testosterone: AR action in muscle, bone, brain, bone marrow; where anabolic effects are prevalent

• DHT: AR action in genitalia, prostate, skin, and hair follicles due to higher expression of 5-alpha-reductase enzyme in these tissues

what enzyme converts testosterone to dihydrotesterone (DHT)?

5-Alpha-reductase

identify the hormones & explain the various steps in the testosterone control mechanism

Hypothalamic-pituitary testicular axis (HPTA)

• hypothalamus makes LHRH (GnRH) and signals the pituitary to release LH/FSH

• LH binds in the leydig cells & increases testosterone synthesis to fuse to the sertoli cells where FSH bins

Feedback control

• Low concentration of testosterone or estradiol causes positive feedback and the body needs to make more (speed up the pulsatile to create more testosterone)

• High concentrations causes negative feedback and the body needs to shut the pathway off (slows the pulsatile down, which its still producing GnRH but tells the pituitary not to do anything with it & not produce more testosterone)

male hypogonadism

testosterone deficiency

• inability to produce sufficient testosterone to maintain sexual function, muscle strength,BMD, and fertility

What are the two basic types of male hypogonadism

• primary: disorder of testes (LH & FSH elevated but testosterone is not produced by the testes)

• secondary: caused by disorder of hypothalamus-pituitary axis

Klinefelter syndrome

primary hypogonadism

• abnormality where two or more X chromosomes are present in addition to one Y chromosome

Hemochromatosis

primary hypogonadism

• too much iron in blood producing testicular dysfunction

Injury or trauma to testicles

primary hypogonadism

not protected by body ,depends on extent of injury

Undescended testicles

primary hypogonadism

• generally self-corrected or may require surgery

Kallmanns syndrome

secondary hypogonadism

• hypothalamus can’t stimulate the release of hormone form the pituitary

• loss of smell & red/green color blindness

Pituitary Disorders

secondary hypogonadism

• tumor on or near the pituitary

radiation/chemotherapy

secondary hypogonadism

Describe the bioavailability of androgens

• poor oral bioavailability

• transdermal DHT has the most bioavailability

explain the structure activity relationship of androgens agonist when it comes to their potency

• 3-keto group

• no 4,5 double bond

• 17-beta-alcohol

what does adding an alkyl chain do to agonist androgens ?

increases oral activity but decreases potency

what are the 3 types of androgen antagonist

• androgen receptor inhibitors

• 5alpha reductase inhibitors

• inhibitors of testosterone

what is the indications for androgen antagonist?

• hormone treatment for prostate cancer (non-curative)

• benign prostatic hyperplasia (BPH)

• hair loss in males

• excessive hair growth (hirsutism) in females

when is hormone therapy used for prostate cancer?

• cancer has spread to far to be cured by surgery or radiation

• reoccurrence of cancer

• before (to shrink) or along with (for high risk reoccurence) radiation

How does hormone therapy work for prostate cancer?

• prostate cancer needs androgens to grow

• hormone therapies: decreases androgens levels or block androgen action

• Androgen Antagonist; combine w/ luteinizing hormone-releasing hormone (LHRH) agonist (Leuprolide & Goserelin) which results in medical castrations

what are the 4 SARs for androgen antagonist ?

• ortho EWG groups on terminal benzene ring (cyano, trifluoro, chloro,nitro)