Module #3: Adrenal Cortex and Reproductive Hormones Flashcards
What is the role of the Adrenal Gland in the endocrine system?
Response to stress
Maintain water/salt equilibrium
Maintain BP
Sympathetic function = “extension of ANS”
What are the 2 regions of the adrenal gland?
Medulla
Cortex
What does the adrenal medulla do?
Release catecholamines –> epinephrine and norepinephrine
What does the adrenal cortex do?
Release aldosterone, cortisol, and dehydroepiandrosterone (DHEA)
What are the 3 layers of the adrenal cortex?
Zona glomerulosa = outer
Zona fasiculata = middle
Zona reticularis = inner
What does the zone glomerulosa do?
produce/secrete mineralcorticoids (ie aldosterone)
What does the zona fasiculata/zona reticularis do?
produce/secrete glucocorticoids (cortisol) and adrenal androgen (DHEA)
What is the first step of hormone synthesis in the adrenal cortex?
cholesterol –> pregnenolone
What is the enzyme that converts cholesterol to pregnenolone?
desmolase
What is the stimulus of the conversion of cholesterol to pregnenolone?
ACTH from anterior pituitary
What happens after cholesterol is converted to pregnenolone?
Pregnenolone can follow 3 pathways to form aldosterone, cortisol, or DHEA
will go to a different region to be converted to the different hormones (each region has specific enzymes for one of the pathways)
Which enzymes do the zona glomerulus (outer layer) contain?
enzymes to convert pregnenolone –> aldosterone
Which enzymes do the zona fasiculata (middle)/zona reticularis (inner) contain?
enzymes that will convert pregnenolone –> cortisol OR DHEA
What happens if there are deficiencies in the adrenal cortex enzymes?
Siginifcant adrenal pathology
How are adrenal cortex hormone production regulated?
Syntehsized @ rate of demand
NOT stored!
How do adrenal hormone levels fluctuate?
Follow Circadian Rhythm Pattern
What are the adrenal hormone stimulus signaling steps (start w/ hypothalamus)?
Hypothalamus releases CRH
CRH stimulates anterior pituitary to release ACTH
ACTH stimulates desmolase activity (cholesterol –> pregnenolone)
What is aldosterone influenced by?
Angiotensin II
ECF (extracellular fluid) K+ levels
What inhibits adrenal cortex hormone production?
Increased levels of cortisol inhibits release of ACTH and CRH = negative feed back loop
Where are glucocorticoids (cortisol) produced?
Zona Fasiculata
Zona Reticularis
What stimulates cortisol secretion?
ACTH from anterior pituitary
Normal Circadian Rhythm
Stress
What is the normal circadian rhythm of cortisol release?
Released between midnight and 8 am –> peak just before awakening
How does stress stimulate the release of cortisol?
Stimulates the release of ACTH
Alter normal circadian rhythm
What inhibits cortisol secretion?
Elevated levels of cortisol inhibits ACTH and CRH
What is the function of cortisol?
Acts as response to normal human stress:
Catabolic to produce/mobilize/store glucose
Maintains fluid volume
Modulates the immune system (anti-inflammatory response)
What are the target tissues of cortisol?
Bone
Adipose (fat) cells
Muscle
Tendon/Ligament/Connective Tissue
Immune System
CNS
Metabolism
Others
What is the action of cortisol on bones?
Stimulate osteoclasts/Ca2+ resorption –> decrease bone density
What is the action of cortisol on adipose cells?
Stimulate lypolysis –> mobilize FFA and glycerol for fuel and production of “new” glucose
Synergistic w/ glucagon, GH, catecholamines
What are the adverse results of cortisol stimulating lypolysis?
FFA are redistributed –> central obesity
Also leads to poor lipid profile
What is the action of cortisol on muscle?
Stimulates proteolysis –> mobilize amino acids for fuel and production of “new” glucose
What is the adverse result of cortisol on muscle?
Muscle wasting/weakness
Loss of lean body mass
What is the action of cortisol on tendon/ligaments/ connective tissue?
catabolic effect –> inhibits fibroblasts/collagen production
What is the adverse result of cortisol on tendon/ligaments/ connective tissue?
Ligament/Tendon failure
What is the beneficial action of cortisol on the immune system?
Anti-inflammatory –> decrease PGs, histamine, bradykinin, serotonin
What is the adverse action of cortisol on the immune system?
Poor wound healing/immune defenses –> impair T-lymphocytes, eosinophils, basophils, ILs, cell mediated immune response, antibody response, etc
What type of cortisol therapy is considered ok?
5 day taper
problem when its longer or high dose
What is the action of cortisol on the CNS?
Alters perception/mood
Negative feedback to hypothalamus (CRH)/anterior pituitary (ACTH)
What is the action of cortisol on metabolism?
Alters intermediary metabolism to produce, mobilize, store glucose
Liver = gluconeogenesis/glycogenesis
Optimizes/enhacnes effect of glucagon (lipolytic, impair glucose uptake) and catecholamines
Why does cortisol alter intermediary metabolism to produce/mobilze/store glucose?
Trying to save glucose for CNS survival –> stress response
What does gluconeogenesis do?
Uses FFA, glycerol and amino acis to form “new” glucose”
What is glycogenesis?
Glucose is stored as glycogen
What are the other effects of cortisol in the body?
Vasoconstriction/bronchodilation –> optimizes/enhances effect of caetcholamines
Fetal lungs –> surfactant production and lung development
Enhances bodes ability to tolerate stress –> cold, heat, trauma
Where are mineralcorticoids (aldosterone) produced?
Zona glomerulosa (outer)
What is the function of aldosterone?
Increase blood volume and BP by regulating renal sodium resorption = primary
Decrease plasma potassium
Increase plasma pH –> alkaline
How does aldosterone regulate renal sodium resorption?
Increases Na+ resorption in distal nephrone
What is the consequence of increasing Na+ resorption?
Increase H2O absorption (gradient follows Na+)
Facilitates K+ excretion –> decreases plasma K+
Facilitates H+ excretion –> increase plasma pH (more alkaline) and decreases urine pH (more acidic)
Describe the role that aldosterone has been suggested to play in vasoconstriction
Research suggests aldosterone is produce/secreted by non-Adrenal tissue and have paracrine effect –> aldosterone’s peripheral release contributes to vasoconstriction of blood vessels
What stimulates the release of aldosterone?
ACTH (not as influential as angiotensin II/K+ levels)
Angiotensin II
Hyperkalemia
Which system is angiotensin II involve in?
Renin-angiotensin system
What does the Renin-Angiontensin system do?
Slow hormonal system of BP regulation
Sensory cells in the kidneys monitor perfusion pressure and Na+ content of blood
What stimulates the release of renin from the kidney?
Decreased blood volume
Decreased Na+ concentration
Which cells release renin in the kidney?
Juxtaglomerular cells
What does renin do?
Trigger cascade that eventually produces angiotensin II
Where does the conversion of angiotensin to angiotensin II happen?
Blood stream
What is the enzyme that catalyzes the conversion of angiotensin to angiotensin II and where is it produced?
ACE = angiotensin- converting enzyme
produced in lungs
Clinically, what do ACE inhibitors do?
block the conversion of angiotensin –> angiotensin II –> lower BP
What does angiotensin II do?
Stimulate the production/secretion of aldosterone
What does hyperkalemia do?
Stimulates release of aldosterone from adrenal cortex
Does the K+ mechanism occur independently or dependently from the renin system?
Independently
What inhibits aldosterone secretion?
Hypernatremia = increased Na+ d/t overproduction or loss of H2O
ANP = atrial natriuretic peptide
Elevated ACTH levels (negative feedback)
Where does ANP come from?
Released in atria in response to increased BP
What does ANP do?
Inhibits renin release
Increases excretion of Na+/H2O –> opposite of aldosterone
Relaxes smooth muscles of smooth muscle vascular system –> dilation decreases TPR
What are the adrenal androgens?
DHEA = dihydroepiandrosterone
Androstenedione
Where are the adrenal androgens produced?
Zona Fasiculata (middle)
Zona Reticularis (inner)
What are androgens?
Sex hormones associated w/ the development/maintenance of male sexual characteristics –> deep voice, hair, baldness, etc
Are androgens only important in males?
No, also critical for females
What do androgens do in females?
Maintain muscle mass
Maintain bone density
Sexual desire
Sense of well being
Estrogen production
What happens when females have low androgen levels?
Low Libido
Muscle/bone mass loss
Fatigue
In males where are androgens produced?
Testes = testosterone
Adrenal cortex = DHEA/Androstenedione (later converted to testosterone)
In females where are androgens produced?
Ovaries = testosterone
Adrenal cortex = DHEA/Androstenedione (later converted to testosterone)
In females what happens to the majority of testosterone?
Converted to estrogen
Which adrenal gland androgen is produced in greater quantity?
DHEA
What happens to DHEA and androstenedione?
Converted to testosterone in periphery
Which tissues are involved in DHEA and androstenedione conversion?
Gonads
Adipose tissue
Sebaceous glands
Hair follicles
Prostate
In males does the conversion of DHEA and andostenedione contribute significantly to overall testosterone levels?
No
Most testosterone is produced in testes
In females does the conversion of DHEA and androstenedione contribute significantly to overall testosterone levels?
Yes
Approximately 50% of circulating testosterone
What is the most abundant circulating hormone in the body?
DHEA
What kind of androgen is DHEA?
“Weak Androgen” –> poor binding affinity to androgen receptors in body
What role does the adrenal gland androgens have in females?
Play role in axillary and pubic hair growth
What role does the adrenal gland androgens have in males?
Not a significant role
Gonadal testosterone plays much bigger role in masculinization
What happens in males if there is an excessive amount of adrenal androgens?
Adults = no effect
Pre-puberty = isosexual precocious puberty –> early puberty; definite as < 9 yo
What happens in females if there is an excessive amount of adrenal androgens?
Adults = masculinization effects –> cystic acne, hirsutism, male type baldness, menstrual irregularities, infertility, and/or frank virilization
Pre-puberty = heterosexual precocious puberty –> girls develop secondary male characteristics; defined as < 8 yo
What stimulates adrenal androgen secretion?
ACTH
What inhibits adrenal androgen release?
Cortisol
What are some clinical diseases of the adrenal cortex?
Addison’s Disease
Hyperadrenalism = Cushing’s Syndrome or Cushing’s Disease
Primary Hyperaldosteronism = Conn’s Syndrome
What is Addison’s Disease?
Adrenalcortical insufficiency
Desruction of adrenal cortex –> loss of ALL adrenal cortex hormones
What will the labs of a pt with Addison’s look like?
Elevated ACTH (trying to stimulate adrenal cortex)
Decreased levels of adrenal hormones
What will the labs of a pt with Addison’s look like?
Elevated ACTH (trying to stimulate adrenal cortex)
Decreased levels of adrenal hormones
What are some clinical diseases of the adrenal cortex?
Addison’s Disease
Hyperadrenalism = Cushing’s Syndrome or Cushing’s Disease
Primary Hyperaldosteronism = Conn’s Syndrome
What is the effect of Addison’s on the zona glomerulosa?
Decreased mineralcorticoids (aldosterone) secretion
In addition to dehydration and polyuria what else do you see in pts w/ excessive excretion of Na+ and H2O?
Hypotension
Hyponatremia (Na+ levels)
Decreased blood volume –> circulatory failure
What happens in the body w/ increased K+ and H+ retention?
Hyperkalemia
Metabolic acidosis
What is the effect of Addison’s on the zona reticularis and zona fasiculata?
Decreased glucocorticoids (cortisol) secretion
Decreased adrenal androgens
What are the consequences of decreased glucocorticoid secretion?
Hypoglycemia
Fatigue
Loss of appetite
What are the consequences of decreased adrenal androgens?
Female = decreased axilla/pubic hair
Hperpigmentation –> elevated ACTH –> elevated MSH
Weakness
Anorexia
Weight loss
Nausea
What are the 2 conditions of hyperadrenalism (excessive adrenocortical hormones)
Cushing’s Syndrome
Cushing’s Disease
What is Cushing’s Syndrome?
Excess cortisol of any pathology
What are some of the causes of Cushing’s Syndrome?
Tumor Secreting Glucocorticoids
Prolonged pharmaceutical usage of glucocorticoids
Effects = primarily elevated cortisol levels
What is Cushing’s Disease?
Excessive ACTH –> excess cortisol
What is a cause of Cushing’s Disease?
Tumor in pituitary –> excessive/elevated ACTH
Besides elevated cortisol what else can be elevated in pts w/ Cushing’s Disease?
Mineralcorticoids
Adrogenic Effects
What are the effects of increased glucocorticoids?
Poor would healing = decreased immune function
Hyperglycemia (d/t increased cortisol) –> glycosuria
Muscle wasting (d/t increased protein catabolism)
Osteoporosis (d/t increased cortisol)
Central Obesity (face/trunk = round, Buffalo Hump)
What are the effects of increased mineralcorticoids?
Hypertension (d/t elevated aldosterone and cortisol)
What are the effects of increased adrenal androgens?
Females:
Virilizition
Menstrual Disorders
What causes primary hyperaldosteronism aka Conn’s Syndrome?
Tumor of adrenal cortex that secretes aldosterone?
What are the results of Conn’s Syndrome?
Hypertension (increased ECF volume) –> increase Na+ and H2O reabsorption in kidneys
Hypokalemia –> increase K+ secretion in kidneys
Metabolic alkalosis –> increased H+ secretion in kidneys
What determines fetal sexual differentiation?
Sex Chromosomes:
Males = XY
Females = XX
Describe fetal male genitalial differentiation
Y chromosome secretes SRY antigin –> gonads into testes
Testes secrete testosterone:
Wolffian Duct –> epididymis, vas deferens, seminal vesicle
Sertoli Cells –> MIH (Mullerian-inhibitng factor) prevents Mullerian Duct from becoming female
Prostate converts Testeserone to DHT (dihydrotestosterone) –> scrotum, penis, prostate gland
Describe fetal female genetalial differentiation
NO SRY antigen –> glands into ovaries
No male hormones:
MIH not release –> Mullerian duct becomes fallopian tubes, uterus, vagina
Wolffian duct DOESN’T become epididymus , vas deferens, and seminal vesicle
What are the primary male sex organs?
Testes
What does the testes do?
Produce testosterone
Produce spermatogenisis –> spermatozoa
What are the consequences of decreased aldosterone secretion?
Excessive excretion of Na+ and H2O in Urine –> dehydration and polyuria
Excessive retention of K+ and H+
What are the 2 hormones that are required to produce spermatozoa?
Testosterone
FSH
Where is testosterone synthesized in the testes?
Interstitial Cells of Leydig
What are the physiological effects of testosterone?
Anabolic Effects
Androgenic Effects
What are the anabolic effects of testosterone?
Stimulate GH secretion –> IGF-1 release
@ End of puberty promotes mineralization (closure) of growth plates
Stimulates protein synthesis in muscles
What are the androgenic effects of testosterone?
Regulate development and maintenance of male accessory sex organs
Plays role in differentiation of male productive tract and brain
@ Puberty = development of secondary males sexual characteristics
Plays role in libido/potency (spermatogenesis)
What are the secondary male sex characteristics developed @ puberty?
Laryngeal changes = deep voice
Growth of facial, pubic, axillary hair
Receding hair pattern @ temples
Increase muscle mass (protein anabolism)
Stimulate growth spurt
Influence sex drive
Influence sexual behavior
Increased sebaceous gland excretion –> acne
What happens to testosterone when adults age?
Gradually decreases (slow and steady)
What does GnRH do?
Stimulates LH and FSH release from anterior pituitary
What does LH (leutinizing hormone) do?
Stimulates the synthesis and secretion of testosterone from testes
What inhibits LH?
Increased blood levels of testosterone (negative feedback loop)
What does FSH do?
Stimulates spermatogenesis (sertoli cells)
Stimulates release of Inhibin from testes
Approximately when does male puberty occur?
13 - 16
What are the hormones that regulate testes and testosterone?
GnRH:
LH
FSH
What does inhibin do?
Inhibits anterior pituitary from releasing FSH –> spermatogenesis
What does the hypothalamus do during male puberty?
Secretes GnRH in bursts
What does GnRH stimulate in the anterior pituitary during puberty?
Increased Release of FSH and LH
In males what does increased LH do?
Stimulates testes to produce and release testosterone
In males what does the increased testosterone do during puberty?
Stimulates androgenic/anabolic changess
Increased blood levels of testosterone inhibit release of GnRH from anterior pituitary (negative feedback)
In males during puberty what does increased FSH do?
Initiates spermatogenesis
Stimulates secretion of inhibit (cells of sertoli) –> inhibits FSH release from anterior pituitary (negative feedback)
What happens if there is atrophy of the testes @ the time of normal puberty?
Sex organs remain small
Secondary sex characteristics fail to develop
What happens if there is atrophy of the testes after puberty?
Sterility –> no spermatogenesis
Testosterone production decreases –> atrophy of secondary sex organs (penis, scrotum, prostate)
What are the female primary sex organs?
Ovaries
What do the ovaries do?
Oogenesis –> production of female germ cells (ova)
Produce: estrogen and progesterone
What is estrogen involved in?
Menstrual Cycle
Fertilization
Puberty
Bone Metabolism ((+) effect on bone density)
Blood Chemistry
CNS Responses
What does estrogen do during the menstral cycle?
Accelerates the maturation of ovarian follicles right before ovulation
Thickens Endometrium
Increases Uterine Muscle Contraction
Changes properties of vagina to assist in fertilization
Prepares mucous plug of the cervical os to allow sperm to enter the uterus
What is the role of estrogen during fertilization?
Prepare the sperm to penetrate/fertilize ovum
Regulate the speed that the ovum travels in Fallopian tube
What does estrogen do to females during puberty?
Stimulate ductal development in breast
Induces changes in the vagina
Changes in subucatenous fat distribution
Synergistic w/ adrenal androgens –> axillary/pubic hair
Accelerate epiphyseal plate closure
Regulate development and maintenance of female secondary sex characteristics
What are the female secondary sex characteristics?
Narrow Shoulders
Wide Pelvis
Wide Carrying Angle
Etc
What are functions of estrogen on bone density?
Accelerate epiphyseal plate closure @ puberty
Increase Ca2+ retention in the kidney
Increase osteoblastic activity
What is estrogens role in blood chemistry?
Positive effect on blood cholesterol (increase HDL/VLDL; decrease LDL)
Increase coagulation –> increase risk of thrombosis w/ excessive levels
Increase Na+ and H2O retention in kidneys
What does estrogen do in the CNS?
Influence sexual response, sexual behavior, mood
What are the major functions of progesterone?
Prepare female genitalia for implantation/maturation of fertilized ovum
Maintain pregnancy
What is the target tissue of progesterone?
Uterus
What does progesterone do in the uterus?
Stimulates the growth of uterine muscles (myometrium)
Increase blood supply to the endrometrium
Promotes implantation by decreasing uterine muscle activity
Narrows cervical os and changes mucous plug to prevent sperm from entering uterus
Increases basal body temperature (metabolic)
When is progesterone given as birth control?
During follicular phase
How does progesterone work as a contraceptive?
Inhibits LH –> inhibit ovulation
Inhibit the effects on cervical os and mucous plug
When given in combination, what does progesterone and estrogen do?
Prevent LH/FSH release
21 days on; 5-7 off = menstrual flow
What are the effects of high doses of progesterone?
Anesthetic effect on CNS
Increases susceptibility to epileptic episodes
Increase basal body temperature
When do you observe a decrease in progesterone?
Postpartum
Luteal Phase
Clinically what is decreased levels of progesterone suspected to be involved in?
Postpartum depression
PMS
What is the general overview of the Menstrual cycle beginning w/ Day 1 as the start of menstruation?
Day 1 - 14 = Follicular Phase
Day 14 = Ovulation
Days 14 - 28 = Luteal Phase
How long does a normal mentruation last?
2 - 6 days
What happens during the follicular phase?
Endrometrium thickens
Approximately 20 follicles mature (FSH) –> 1 becomes dominant and others degenerate
Days 12 - 13 estrogen levels increase (+ feedback on LH) –> stimulate surge of LH
What happens during ovulation?
Surge of LH –> ovum release from follicle
Cervical mucous has thinned (spinnbarkeit)
Cervical Os opens slightly (allow sperm to enter uterus)
What happens during the luteal phase?
Follicle = corpus luetum
Corpus Luetum –> increased progesterone/estrogen
Progesterone releaxes uterine muscle activity –> implantation if ovum is fertilized
No fertilization –> estrogen/progesterone fall –> decrease blood flow to endrometrium
Ischemia of endometrium –> menses (break down of uterine lining and bleeding)
Hormonally what is happening during the early follicular phase?
GnRH = released from hypothalamus
GnRH stimulates release of FSH/LH from anterior pituitary
LH/FSH stimulate production of estrogens
Estrogens enter blood stream –> (+) feedback on FSH receptors in follicles
What is the specific role of LH in the production of estrogens?
Stimulates production of androgens (androstenedione/testosterone) in the ovaries
(internal cells of the follicles)
What is the specific role of LH in the production of estrogens?
Stimulates production of aromatase in ovary (grandulosa cells of the follicles) –> converts androgens to estrogens
Hormonally what is happening during the mid-follicular phase?
Dominant follicle emerges continues to produce estrogen ( (+) feedback)
Apoptosis of non-dominant follicles
Hormonally what is happening during late-follicular phase?
Estrogen levels increase –> ( (+) feedback on release of LH)
Surge of LH
What happens if there is a slow surge of LH or no surge of LH?
Ovulation doesn’t occur
Hormonally what is happening during the Luteal Phase of the Menstral Cycle?
Ovum released –> Corpus Luetum
Corpus Luetum secretes progesterone and estrogen
Progesterone/estrogen INHIBIT release of FSH/LH ( (-) feedback) –> decrease in progesterone/estrogen as luteal phase progresses
Low levels of progesterone/estrogen –> constriction of blood flow to endometrium –> menses –> new cycle
What happens if fertilization occurs?
Progesterone/estrogen levels stay elevated
Where are the pregnancy hormones produced?
Placenta
hCG produced from syncytioltrophoblast until placenta is fully developed
What is hCG?
Human Chorionic Gonadotropin
What is the function of hCG?
Maintains production of estrogen/progesterone in corpus luetum until placenta takes over
Suppresses follicle maturation in maternal ovaries
What can hCG be used for?
Pregnancy Test
Measurable 6 - 8 days after conception
Which hormones does the placenta produce?
Progesterone
Estrogen
Corticotropin Releasing Hormone (CRH)
Human Placental Lactogens (hPLs)
What does CRH do?
Plays role in regulation of birth
What happens to the concentration of CRH during pregnancy?
Increases
What is the rate of concentration of CRH critical for?
Timing of birth
What happens if there is an increased rate of CRH?
Contributes to premature birth
What happens if there is a decreased rate of CRH?
Contributes to delayed birth
What does hPL do?
Plays role in lactation and physical growth
When does menopause typically occur?
45 - 55
What happens during menopause?
Ovarian tissue gradually ceases to respond to FSH/LH
Decreased levels of estrogen/progesterone
What happens to the menstrual cycle when the ovaries stop responding to FSH/LH?
Irregular Cycles
Gradually Stop Cycle
What happens during menopause when estrogen/progesterone levels decrease?
Regression of secondary sex characteristics
Atrophy of breast tissue
Thinning of pubic/axillary hair
Accessory sex organ Atrophy:
Fallopian tubes shrink
Vaginal epithelium thins (decreases
secretions)
Exteneral genitalia shrinks
Mood changes
Increase risk of osteoporosis –> loss of estrogen
Increased Cardiovascular risks –> loss of estrogen
