Steroid hormones

flow of the endocrine system

hypothalamus --> anterior pituitary --> endocrine gland (gonads) --> target organ

main hypothalamic hormone for lifecycle course

-GNRH (gonadotropin releasing hormone

peptide hormones (for lifecycle)

-LH

-FSH

-hCG

what produces the peptide hormones: LH, FSH, hCG

- LH, FSH: anterior pituitary

- hCG: placenta during pregnancy

sex steroids families we need to know for this class

- estrogens (18 C)

-progestogens (21 C)

- testosterone/androgens (19 C)

-corticosteroids

what secretes sex steroids

endocrine glands

What hormones tell the gonads what to do/what to produce

peptide hormones

what are peptide hormones synthesized as? what does this mean?

prohormones --> need to be cleaved to be activated

where are peptide hormones stored

vesicles --> regulates secretion

Are peptide hormones hydrophilic or hydrophobic?

hydrophilic --> can freely circulate in blood (no binding protein needed)

peptide hormones bind cell surface receptors and transduce signal via ________

secondary messengers

Many pituitary hormones signal through a________________ on the cell surface and use phosphorylation to signal.

G-protein coupled receptor --> peptide hormone signaling

what do LH and FSH stimulate the release of

steroid hormones (estrogen, progestogens, testosterones from gonads)

What sex hormone do the adrenal glands secrete? what stimulates this release?

DHEA

-stimulated by the pituitary hormone CRH and ACTH

What stimulates the release of LH and FSH? What determines how much is released

GNRH

-pulse pattern determines how much is released (not the amount og GNRH

Where does GNRH come from?

the hypothalamus

How is the GNRH secreted?

In a pulsatile fashion – the rhythm of the pulses indicates how much LH and FSH should be released

Steroid hormones are synthesized from ____

When are they released?

cholesterol

-released immediately after synthesis

Are steroid hormones lipophilic or hydrophilic?

- lipophilic --> require carrier proteins (made by liver) to travel in the blood

what carrier protein is estrogen and testosterone bound to

SHBG (sex hormone binding globulin)

what carrier protein are progesterone and corticosteroids bound to

CBG (corticoid binding globulin)

steroid hormone signaling pathway, what does this do?

bind to intracellular receptor (modify gene transcription) --> big actions but take a while to have them (slower process than peptide hormones --> secondary messangers)

where is the steroid hormone nucleus derived from

cholesterol

rate limiting step of sex steroid biosynthesis

CYP11A1

-cholesterol transformed into pregnenolone (which then goes on to make progesterone)

The same pathway that goes from cholesterol to progesterone goes on over to ____ and ______

- cortisol

- aldosterone

Overall, cholesterol goes through ______ everyday to make many other chemicals

progesterone

What changes the affinity of binding between estrogen and testosterone.

the amount of SHBG in the blood --> (More SHBG means more bound estrogen relative to testosterone, and visa-versa.)

should free or total testosterone be measured to measure the amount of testosterone in the body

Free

what is the predominant path of steroid action on a cell

classical/genomic pathway --> transcription of target gene

describe the classical genomic pathway of steroid hormone action

- Steroid enters the cell and binds to a nuclear receptor (NR) -->

- releases an inhibitory heat shock protein (HSP). -->

- Steroid bound receptor dimerizes and enters the nucleus -->

- binds to a steroid response element (SRE) and activates transcription of target gene.

which steroid pathway is faster, nonclassical or classical

nonclassical --> does not involve nuclear receptor binding to genomic DNA

in the nonclassical nongenomic pathway, where doe the hormone bind to the receptor

at the membrane (faster pathway)

two mechanisms of actions of sex steroids...what are their actions

-classical/genomic pathway

-nonclassical/nongenomic call membrane

- decrease inflammation

-alter gene transcription

what are corticosteroids derived from

cholesterol

two main progestogens

- progesterone (relative potency: 100)

- 17(-hydroxyprogesterone (17OHP) (relative potency: 50)

action of progestogens

- support pregnancy

- involved in mammary gland development

what are progestins? example

synthetic progestogens

-Medroxyprogesterone acetate (MPA)

clinical use of progestins

- primary ingredient of contraception (tricks body into thinking its pregnant)

-hormone therapy

Anti-Progestins examples

- Mifepristone (aka RU-486)

- Ulipristal acetate

what are anti- progestogens

- Partial agonists that function as antagonist in the presence of progesterone

clinical use of Mifepristone

- Emergency contraception

- medical abortion

- heavy menstrual bleeding

clinical use of ulipristal acetate

- Emergency contraception

- uterine fibroid reduction

major categories of estrogens, when are they predominant?

- estrone: after menopause

- estradiol: during childbearing years (people with two functioning ovaries)

- Estriol: pregnancy

How many isoforms do estrogen receptors have? What do they function as?

-two

- function as dimers

what is a dimer? example of an estrogen dimer

receptors that act differently in different tissues

- tamoxifen

tamoxifen effect of uterus and breast

- in breast, it is an estrogen antagonist and is very important in breast cancer treatment.

- in the uterus, it is an estrogen agonist and can cause uterine cancer! --> hysterectomy to prevent cancer

action of estrogens

- stimulates breast and endometrial tissue

- supports bone health

what are estrogens used for

- menopausal symptoms

- improve symptom profile of contraceptives

- transgender care

- fertility treatment

- some gynecologic disorder

what are Estrogen-receptor modulators and specialized estrogens/antiestrogens used for

cancer prevention and treatment

drug reactions of estrogens

- endometrial cancer (when taking estrogen with no progesterone in body)

- breast cancer

- hypercoagulability

- increased risk of blood clots: VTE

categories of androgens

- testosterone

- Dihydrotestosterone (DHT) (most potent)

- Androstenedione

- Dehydroepiandrosterone (DHEA)

androgens action

- promotes growth and development of sex organs

- maintains male secondary sex characteristics

- increases muscle mass and bone density

what are androgens used for

medications used for hypogonadism, transgender care and misused (along with GH) in athletics

ADR (adverse drug reaction): Androgens

- hypertension

- dyslipidemia (abnormal cholesterol)

- cardiomegaly

- renal disease

- hypogonadism

- azoospermia

- gynecomastia (man boobs)

- acne

- neuropsychiatric disease.

what are Androgen Receptor antagonists used for

-treatment for prostate cancer and hyperandrogenism

Androgen Receptor antagonists adverse effects

Sexual dysfunction, bone fractures

what is 5a-reductase inhibitor used for

- Used to treat benign prostate hypertrophy (BPH)

- male-pattern hair loss

- excess hirsuitism

5a-reductase inhibitor adverse effects

- Sexual dysfunction

- depression

5a-reductase inhibitor MOA

blocks the enzyme that converts Test to DHT which has specific effects

How else could we control sex hormone secretion?

GNRH manipulation

what are GnRH agents used for

- reproductive technology (infertility)

- endometriosis

- uterine fibroids

- transgender care

GnRH agent ADR

- osteoporosis (effect on bone density)

- hot flashes

- nausea

- edema

- acne

What do GnRH agonists do

-increase pulse pattern but it stops LH and FSH from being secreted

what causes hypogonadism

absence of GnRH neurons --> usually presents with anosmia also (inability to smell)

What happens if there is continuous (not pulsatile) GnRH stimulation to the pituitary cells?

- Down regulates GnRH receptors and stops gonadotropin secretion