HPG Axis, Gonadal Hormones And Inhibitors Flashcards
What are primary endocrine organs?
Pineal gland
Hypothalamus
Pituitary gland
Thyroid/parathyroid glands
Thymus
Adrenal gland
Pancreas
Testes/ovaries
Placenta
What are secondary endocrine organs?
Skin
Heart
Liver
Stomach
Kidney
Small intestine
The control of metabolism, growth, and reproduction is mediated by a combo of neural and endocrine systems located in the ________ and ________
Hypothalamus, pituitary gland
Which endocrine organ consists of an anterior and posterior lobe?
Pituitary
Which sole anterior pituitary hormone acts directly on target tissues?
Prolactin (PRL)
GH, TSH, ACTH, LH, and FSH are secreted by? What two hormones do they stimulate?
Anterior pituitary
Estrogen and testosterone
Which two hormones are secreted by the posterior pituitary?
ADH and oxytocin
ADH:
Where is it produced?
Released?
Targets?
Effects?
Hypothalamus
Posterior Pituitary hormone
Kidneys, sweat glands, and circulatory system
Water balance
Oxytocin:
Where is it produced?
Released?
Targets?
Effects?
Hypothalamus
Posterior pituitary hormone
Female reproductive system
Uterine contractions during birth
Which hormone is released by the hypothalamus to stimulate sex hormone/gamete production? Which anterior pituitary hormone?
GnRH
FSH/LH
Which hormone is released by the hypothalamus to stimulate thyroid hormone production? Which anterior pituitary hormone?
TRH
TSH
Which hormone is released by the hypothalamus to stimulate milk production? Which anterior pituitary hormone?
PRH
PRL
Which hormone is released by the hypothalamus to stimulate IGF production? Which anterior pituitary hormone?
GHRH
GH
Which hormone is released by the hypothalamus to stimulate glucocorticoid production? Which anterior pituitary hormone?
CRH
ACTH
What is LH’s effect in females in the ovaries?
Increased estrogen and progesterone production
What is LH’s effect in males in the testes?
Testosterone production
Gonadotropin releasing hormone (GnRH) causes secretion of which two gonadotropins?
FSH and LH
Pulsation GnRH release occurs and is responsible for stimulating LH and FSH production during the ____ and ________ period.
Year 2-puberty: GnRH ____________ and pituitary has ____ sensitivity.
Just before puberty, there is ___________ frequency and amplitude of GnRH, and in early puberty, pituitary sensitivity to GnRH _______.
Fetal, neonatal
Falls off, low
Increased, increases
what is gonadorelin?
how is it used?
a more potent, synthetic acetate salt of GnRH
when used as a single dose helps initiate puberty. as a pulsatile dose treats GnRH-deficient infertility by stimulating FSH and LH secretion. as a sustained long-acting dose inhibits gonadal function in children with early puberty and women who require ovarian suppression
what are the names of the drugs that are GnRH agonists?
what is the MoA?
Leuprolide
Goserelin
Histrelin
Nafarelin
Triptorelin
inhibits gonadotropin release to suppress:
ovulation
gynecologic disorders
advanced prostate cancer
early pubertal transgender adolescents
what are adverse effects of GnRH agonists?
symptoms of menopause
long-term treatment bone loss and osteoporosis
gynecomastia
reduced libido
In men with prostate cancer and children with precocious puberty, the first few weeks of GnRH therapy can temporarily ___________ the condition (cause a _____)
exacerbate, flare
What are the GnRH antags?
Ganirelix
Cetrorelix
Degarelix
which GnRH antags suppress endogenous gonadotropin production during ovulation induction?
Ganirelix and Cetrorelix
which GnRH antag treats advanced prostate cancer?
Degarelix
GnRH antags __________ a tumor flare when used for prostate cancer and may be less likely to cause ______________ syndrome when used for ovulation induction
do not cause, ovarian hyperstimulation
what is FSH’s function in male/female?
male: regulates spermatogenesis
female: follicle development
what is LH’s function in male/female?
Male: stimulates testicular androgen production
female: works with FSH to regulate ovarian steroidogenesis
all ovulation induction protocols that use gonadotropins include:
Gonadotropin production is _______ by administration of a GnRH agonist or antag
Follicle development is driven by daily injections of a preparation with ____ activity
The final stage of oocyte maturation is induced with an injection of ___ or __________
inhibited
FSH
LH, human chorionic gonadotropin (hCG)
what is menotropin and how is it produced?
mixture of FSH and LH purified from the urine of postmenopausal women
what is Urofollitropin and how is it produced?
a FSH analog produced from purified urine of postmenopausal women
what are the 2 recombinant forms of human FSH?
follitropin alpha and follitropin beta
what is the role of hCG and how is it produced?
supports the fetus in early pregnancy by activating LH receptors
purified from human urine
what is Lutropin?
a recombinant form of human LH
what is the main antagonist of prolactin?
dopamine
what are the D2 R agonists used as prolactin antagonists? why do we use them?
**Bromoctriptine, cabergoline, and pergolide
prolactin-secreting adenomas cause hyperprolactinemia which leads to infertility and galactorrhea (milk production). D2 agonists help reduce prolactin concentrations. they can also treat acromegaly (excessive growth hormone)
what are the two posterior pituitary gland (neurohypophysis) hormones?
ADH and oxytocin
how do we use oxytocin?
how do we use atosiban?
it stimulates uterine contraction and can induce labor
blocks the oxytocin receptor to suppress preterm labor (not FDA approved)
what is the ADH hormone and it’s MoA?
Vasopressin binds to V2 Rs to increase insertion of water channels in the kidney to have a antidiuretic effect
what is Desmopressin and it’s use?
what are conivaptan and tolvaptan and their use?
V2 R agonist: used for pituitary diabetes insipidus (inability to regulate the body’s level of water)
V2 R antags: offset fluid retention due to excess vasopressin
Summary:
what are the gonadal hormones?
what are SERMS?
what do antiandrogenic drugs do?
estrogen, progestin, and testosterone
selective estrogen receptor modulators: modify function of estrogen
treat prostate cancer and benign prostatic hyperplasia in men and androgen excess in women
what is tamoxifen?
what is it used for?
how is it used prophylactically?
SEs?
a SERM: estrogen R antag
treating breast cancer - blocking estrogen R prevents cell proliferation by inhibiting the estrogen response element
can reduce the chance of breast cancer for very high risk women
hot flushes and increased risk of venous thrombosis
what is fulvestrant?
why/when do we use it?
a full estrogen antag
treat breast cancer if pt is resistant to tamoxifen
what drug class is anastrozole?
use?
competitive aromatase inhibitor
treat breast cancer
how can GnRH agonists effect estrogen?
androgen?
inhibit estrogen production
inhibit androgen production
what is flutamide? what is it used for?
non-steroidal competitive antagonist of androgen receptors which treats prostate carcinoma
what is finasteride’s effect on androgen?
uses?
inhibit androgen R to inhibit dihydrotestosterone production
treats benign prostatic hyperplasia and prevents hair loss in men
what is ketoconazole’s effect on androgen/gonads? what can it treat?
inhibits adrenal and gonadal synthesis to treat steroid-responsive prostate cancer
when properly regulated by FSH and LH, each menstrual cycle consists of:
follicular phase: follicle in ovary matures and secretes estrogen
ovulation: release ovum and transforms to secrete progesterone
luteal phase: if ovum is not fertilized and implanted, egg degenerates
menstruation: the proliferated uterine endometrium is shed
during most of the menstrual cycle, estrogen and progesterone have a negative feedback mechanism to inhibit the hypothalamus from producing _______ and the anterior pituitary from producing ________ which eventually prevents further production of ____________ by the ovary.
on the contrary, around day 12-14, estrogen and progesterone have a positive feedback mechanism to stimulate the production of these pathways
GnRH, FSH and LH, estrogen and progesterone
Estrogen is produced by the _____, whereas progesterone is produced by the _________. Estrogen’s production is regulated by ___, whereas progesterone’s production is regulated by ___.
Estrogen cause enlargement of the _____ and _____ during pregnancy, whereas progesterone causes reduction in the contractility of the ______ and stimulates the growth of __________
follicle, corpus luteum
FSH, LH
uterus, breasts, uterus, mammary glands
which CYP enzyme is essential for estrogen production?
CYP19 (aromatase)
Estrogen is essential for female ___________ such as growth of the __________ during childhood and the __________ associated with puberty.
It modifies serum ______ levels and reduces bone ________.
It enhances the _________ of blood and increase plasma __________ levels while reducing _________ cholesterol and increasing _______ cholesterol
reproductive development, genital structures, growth spurt
protein, resorption
coagulability, triglyceride, LDL, HDL
what is Premarin and how is it used?
mixture of estrogens that is used orally for hormone replacement therapy (HRT)
which synthetic estrogens have high bioavailability?
ethinyl estradiol and mestranol
why do we give women estrogen as HRT?
if they have estrogen deficiency caused by ovarian failure, menopause, or removed ovaries. it also prevents bone loss and osteoporosis
T/F medroxyprogesterone has improved oral bioavailability compared to progesterone, but does not support pregnancy
True
why is progestin always given with estrogen in HRT?
to prevent estrogen-induced endometrial cancer (breast cancer)
what drug class are raloxifen and bazedoxifene?
what do they prevent/treat?
SEs?
SERM
osteoporosis in postmenopausal women and reduce the chance of breast cancer in very high risk women
hot flushes and venous thrombosis (same as tamoxifen)
what is clomiphene used for? MoA?
induce ovulation in anovulatory women who wish to become pregnant by blocking estrogen Rs in pituitary to reduce negative feedback to increase FSH and LH output
what is exemestane?
use?
an irreversible aromatase inhibitor to treat breast cancer
what is danazol?
what does it treat?
inhibitor of several P450s and a weak partial agonist of progestin, androgen, and glucocorticoid Rs
treats endometriosis (uterine cells grow outside uterus) and fibrocystic disease of the breast (painful, lumpy breasts)
what drug class is mifepristone?
use?
what is it combined with?
progesterone and glucocorticoids antag
abortifacient up to 49 days from last menstrual period
it is combined with misoprostol, a prostaglandin analog
Testosterone is synthesized from ________ and ____________.
In the plasma, it is partly bound to _________, a transport protein.
It is converted in several organs to _________, which is the active hormone in those tissues
progesterone, dehydroepiandrosterone (DHEA)
sex hormone-binding globulin
dihydrotestosterone (DHT)
what type of target genes does testosterone modulate?
AR target genes
T/F testosterone attributes to male-pattern baldness
true
testosterone is labeled as an androgen… what can androgens be used to treat?
RBC production in certain anemias and promote weight gain in pts with wasting syndromes (AIDS)
T/F testosterone given orally can have long-lasting effects comparable to injectable formulations
false, little effect due to rapid hepatic metabolism
how does excess androgen effect women?
what about men?
causes hirsutism, enlarged clitoris, deepened voice, and menstrual irregularity
causes gynecomastia, testicular shrinkage, and infertility
high doses of anabolic steroids can cause?
cholestatic jaundice, elevated liver enzymes, and liver tumors
how is spironolactone involved with androgen and what does it treat?
it inhibits androgen Rs to treat hirsutism (facial hair growth) in women
suppression of gonadotropin secretion, especially ___, reduces the production of ________. This can be caused using the drug _____ which can treat _________.
LH, testosterone
leuprolide, prostatic carcinoma
what two GnRH R antags are approved for advanced prostate cancer?
abarelix and degarelix
