Endocrinology - Final Exam Study Material on Sex Hormones & Fertilization

What is the genetic sex for Maleness? Femaleness?

XY

XX

What are the 3 cells of the Testes (Gonadal sex maleness)?

1) Germ Cells

2) Sertoli cells

3) Leydig cells (Interstitial cells)

What are the 3 cells of the Ovaries (Gonadal sex femaleness)?

1) Germ cells

2) Granulosa cells

3) Theca cells

What are the 5 aspects of the internal genital tract for a phenotypical male?

1) Prostate

2) Seminal vesicle

3) Vas deferens

4) Epididymis

5) Testes

What are the 2 aspects of the external genitalia for a phenotypical male?

1) Scrotum

2) Penis

What are the 5 aspects of the internal genital tract for a phenotypical female?

1) Fallopian/uterine tubes

2) Ovaries

3) Uterus

4) Cervix

5) Upper 1/3 of vagina

What are the 4 aspects of the external genitalia for a phenotypical female?

1) Clitoris

2) Labia majora

3) Labia minora

4) Lower 2/3 of the vagina

What is the testis-determining factor?

Y chromosome

The primordial gonads will lead to an ovary due to a lack of what two hormones?

No testosterone

No Anti-Mullerian hormone (AMH)

Ovaries will lead to the development of what ducts?

Mullerian ducts developed & Paramesonephric ducts

What 4 features develops from the Mullerian ducts?

1) Fallopian tubes

2) Uterus

3) Upper vagina

4) Normal external female genitalia

Which cell of the Testis secretes anti-Mullerian hormone (AMH), which leads to mullerian duct regression?

Sertoli cells

Which cell of the Testis secretes Testosterone?

Leydig cells (interstitial cells)

When Testosterone is converted to Dihydro-testosterone by 5 alpha-reductase, what three structures does it lead to?

1) Penis

2) Scrotum

3) Prostate

What ducts does Testosterone lead to the development of?

Wolffian duct development & Mesonephric ducts

What 4 features does the Wolffian ducts develop in to?

SEED

Seminal vesicle

Epididymis

Ejaculatory Duct

Ductus Deferens

The hypothalamus will secrete ____________, which travels to the Anterior Pituitary and finds its receptors on the Gonadotrophs, which then secrete ______________ and ____________ into circulation to the target tissue (teste or ovaries)

Gonadotrophin-Releasing Hormone (GnRH)

Follicle Stimulating Hormone (FSH)

Luteinizing Hormone (LH; interstitial cell releasing hormone)

What mechanism does GnRH use?

Phospholipase C Mechanism

What cell does FSH act on in males? What is the role of FSH in males?

Sertoli cells

stimulate SPERM PRODUCTION (Spermatogenesis)

What cell does LH act on in males? What is the role of LH in males?

Leydig cells

Produce TESTOSTERONE

What are the two functions of testosterone?

1) Support sperm production

2) Generate male characteristics such as muscle mass, enlargement of larynx to generate deep voice; growth of facial/body hair

NOTE: also has function in...

- anabolic effects on muscle/bone

- mental sharpness, concentration, memory

- energy level

- sex drive/libido

- prevents CAD, CHF, HTN

- dilates coronary arteries, maintains healthy cholesterol levels

What is the intratesticular role of the teste? Extra-testicular role?

Sperm production

Develop/Maintain accessory sexual structures

What part of the teste has 500 tubules, 120-300 um and is 500 meter that composes 80% of the testes and functions in SPERM PRODUCTION?

Seminiferous tubules

What three cells are part of the seminiferous tubules?

1) Spermatogonia (stem cells)

2) Spermatocytes

3) Sertoli cells

What are the 4 main functions of Sertoli cells in order to support spermatogenesis?

1) Provide nutrients

2) Form tight junctions (blood-testes barrier; each cell to adjacent 6 cells, permit only certain substances through)

3) Secrete aqueous fluid to transport sperm to epididymis (99% absorbed)

4) Secrete androgen binding protein (ABP) to support levels of testosterone locally (maintains high androgen level of testes)

What hormone is stimulated by FSH so that it negatively feeds back to the anterior pituitary (gonadotrophs) to inhibit FSH production, keeping FSH levels balanced?

Inhibin

What 2 enzymes converts androstenedione to testosterone?

17B-hydroxysteroid dehydrogenase (also 17-ketosteroid reductases)

What enzyme converts testosterone into dihydrotestosterone at target tissue?

5 alpha-reductase

What enzyme converts testosterone into estrogen at the target tissue?

Aromatase

What mechanism of action does Testosterone use?

Steroid hormone mechanism

What are the 3 pieces of the sperm anatomy?

1) Head

2) Mid-piece

3) Tail

What structure is where sperm is stored?

Epididymis

What structure moves sperm from/out of the epididymis?

Ductus deferens/vas deferens

What structure contributes to a fluid rich in fructose, citrate, prostaglandins, and fibrinogen, and leads into the ejaculatory duct?

Seminal vesicle

What structure contributes a milky aqueous solution rich in citrate, calcium, and enzymes that is alkaline, leading into the prostatic urethra?

Prostate gland

Why is it important that the prostate gland contributes the alkaline solution?

Increase sperm motility and neutralize acid secretion

What is the role of FSH in females? (2)

1) Stimulates GROWTH of ovarian follicles in ovary before release of egg from follicle at ovulation

2) Increase estradiol production

What is the role of LH in females in weeks 1-2 of the cycle?

Stimulate ovarian follicles in ovary to produce female sex hormone estradiol

What is the role of LH in females around day 14 of the cycle?

Surge of LH causes ovarian follicle to tear, releasing mature oocyte (egg) from ovary

(OVULATION)

What is the role of LH in females for the remainder of the cycle (weeks 3-4)?

Remnant of ovarian follicle form corpus luteum

-- stimulated by LH to produce progesterone, required to support early stages of pregnancy if fertilization occurs

What cell in the ovary also synthesizes androstenedione which diffuses to nearby granulose cells?

Theca cells

In the granulosa cells, androstenedione is converted to ______________ by 17B-HSD which is then converted into ____________ by Aromatase?

Testosterone

17B-estrodiol

What two enzymes do granulosa cells contain?

17B-hydroxysteroid dehydrogenase and aromatase

In the granulosa cells, androstenedione is converted to ____________ by aromatase which is then converted to ___________ by 17B-HSD?

Estrone

17B-estrodiol

What hormone will bind to the receptor on Theca cells? Granulosa Cells?

LDL

FSH

In which cell type is progesterone made? What is its impact?

Progesterone synthesized in granulosa cell

-- feedbacks/enters (positive?) on the Theca cell in order to make the Androstenedione needed to reenter the Granulosa cell (to make Testosterone & Estrone, then eventually Estradiol)

What days is the follicular phase of the ovarian cycle? What occurs during this phase?

Days 1-14

- Growing follicles (oocyte surrounded by granulosa and theca cells)

What stimulates the follicular phase of the ovarian cycle? What does it produce?

FSH & LH

- Estrogen & Progesterone

What day does Ovulation occur?

Day 14

What days does the Luteal phase occur? What occurs during this phase?

Day 14 - 28

- Ruptured follicle (Corpus luteum) takes over production of progesterone (and estrogen)

Estradiol (Estrogen) Function Summary

- Stimulates growth of ovary & follicles

- Maturation and maintenance of uterus, fallopian tubes, cervix & vagina

- Development of female secondary sex characteristics

- Development of the breasts

- Negative and positive feedback on FSH and LH

- Maintenance of pregnancy

- Stimulation of prolactin secretion

- Anti-osteoporosis

- Regulates body temp (deficiency produces hot flashes)

- Stimulates choline acetyltransferase (prevents Alzheimer's)

- Helps maintain muscle and prevent muscle damage

- Improves sleep

- Maintains collagen in skin

- Reduces risk of cataracts

- Increased blood flow, inhibits platelet aggregation, decreases atherosclerosis

- Improves insulin sensitivity

- Increase metabolic rate

What mechanism of action does estrogen & progesterone use?

Steroid hormone mechanism

What is progesterone made from? Where? How does this change with menopause?

Pregnenolone (produced by ovaries and also by adrenal gland in both males & females)

-- after menopause, adrenals responsible for most production

T/F: Estrogen can be converted to cortisol during fight/flight?

FALSE

- progesterone

What are 9 actions of progesterone?

1) Maintenance of secretory activity of uterus during luteal phase (day 14-28)

2) Help control excessive bleeding/irregular bleeding

3) Development of breasts, particularly glandular tissue

4) Negative feedback FSH and LH

5) Maintenance of pregnancy

6) Decreases contraction of the myometrium

7) Induces thick, sticky cervical mucus

8) Reduce hot flashes

9) Prevents osteoporosis

What conditions first symptom is weight gain, and happens 2-5 years prior to menopause, with FSH levels increasing?

Perimenopause

In perimenopause, at what days should FSH be measured to see if patient getting closer to menopause (no period for 12 straight months), since FSH should normally be low at this time?

Measure FSH at Day 3 - 5

What is the standard treatments of menopause symptoms, has potential harmful and beneficial effects on health, and has two primary forms, estrogen alone and estrogen and progesterone (or progestin)?

Hormone Replacement Therapy (HRT)

Why is estrogen only HRT given to women without a uterus, while estrogen and progesterone is given to those women with a uterus?

Addition of progesterone to therapy prevents estrogen form increasing risk of uterine cancer

What is the number one killer of women?

Heart disease

NOTE -- estrogen & progesterone help protect heart; so when menopause occurs, decreases estrogen & progesterone, increases risk of cardiovascular diseases

T/F: Hormone Replacement Therapy is to be used during menopause

FALSE

-- only during perimenopausal state; NOT menopause

(best candidate those who are in early menopause)

What is the slow progression of ovarian cessation with 12 months without a cycle, with high FSH and low estrogen and symptoms such as hot flashes, excessive sweating, sleep disturbances, irritability, depressive mood, attention deficit disorder, joint/bone pain, headaches, arrhythmias, paresthesia, and weight gain?

Menopause

BONUS: Humans and what other animal are the only ones that go through menopause (cannot reproduce throughout entire life)?

Orca (Killer Whale)

SUMMARY of estrogen and progesterone functions

Bone:

- estrogen required for closure of epiphyseal plates of long bones

- stimulates intestinal calcium absorption, promote osteoblastic activity

Liver:

- Improve circulating lipoprotein profiles, regulates hepatic production of transport proteins

Cardiovascular organs

- Estrogen promotes vasodilation

Integument

- Estrogen and Progesterone increase collagen synthesis and inhibits collagen breakdown by suppressing matrix metalloproteinases (wrinkles)

CNS

- estrogen neuroprotective and has positive effects on angiogenesis

- Progesterone acts on hypothalamus to increase set point for thermoregulation (think ovulation)

- Low progesterone = premenstrual dysphoria (premenstrual syndrome; PMS)

Adipose tissue

- estrogen decreases adipose tissue by decreasing lipoprotein lipase activity and increasing hormone sensitive lipase

- loss of estrogen = accumulation of adipose tissue

What are the two phases of the ovarian cycle? When does ovulation occur here?

1. follicular phase (1-14)

- ovulation (14) -

2. luteal phase (14-28)

What are the three phases of the uterine cycle? When does ovulation occur?

1. menstrual phase/period (1-5)

2. proliferative phase (5-14)

- ovulation (14) -

3. secretory (14-28)

What happens during the period/menstrual (day 1-5) of the uterine cycle?

Endometrium degenerates, leading to menstrual flow

After menstrual flow in period/menstrual phase of uterine cycle, the endometrium begins to thicken due to influence from what?

Estrogen

During the proliferation phase (6-14) of the uterine cycle (between end of period and during ovulation), what stimulates the growth of the endometrium and myometrium? This also induces the synthesis of ________ receptors on endometrial cells?

Estrogen

Induce synthesis of progesterone receptor

During the secretory phase (15-28) of the uterine cycle, after ovulation, the endometrium will increase secretory activity under the influence of what hormones?

Progesterone & Estrogen

With the formation of the corpus luteum in the secretory phase (15-28) of the uterine cycle, what acts upon the endometrium to convert it to actively secreting tissue, which becomes coiled & filled w/ glycogen, more numerous blood vessels, and enzyme accumulation in glands and connective tissue? Why are these changes necessary/important?

Progesterone

Necessary for implantation and nourishment of a developing embryo

What is the goal of combination (estrogen & progesterone) contraceptive? Progesterone only? Morning after pill?

Combination = Prevent OVULATION

Progesterone only = changing mucus and motility of sperm

Morning after = high dose progesterone to changes mucus and motility of sperm

What is a syndrome describing the set of symptoms some women experience after discontinuing hormonal-containing birth control, where there is an androgen rebound effect occurs if ovulation doesn't come back right away, so there is no ovulation, no progesterone, and increase estrogen and testosterones, leading to symptoms such as acne, weight gain/bloating, irregular/absent cycles, heavy cycles, cramps, change in mood, and breast tenderness?

Post Birth Control Syndrome (PBCS)

What is the union of ovum and sperm?

Fertilization

0.002% of sperm ejaculated in the vagina will make its way to the ampullary-ischemic junction of the fallopian tube. What two events must take place after ejaculation before a sperm can be fully functional and capable of fertilization?

1) Capacitation

2) Acrosome reaction

What is the reaction that occurs when a sperm contacts the zona pellucida of an ova, where hyaluronidase (breaks down hyaluronic acid) is released from the acrosome of the sperm facilitating penetration of the outer layer of the ovum (corona radiata and zona pellucida) and subsequent fertilization?

Acrosome reaction

What is the reaction that is a series of enzymatic and biomedical events which occur while sperm are in the female genital tract prior to fertilization, with the result being that the sperm are hypermobile and have destabilized plasma membranes facilitating initiation of the acrosome reaction (cleaning off head of sperm as travels through reproductive tract)?

Capacitation

What is the fast block to polyspermy?

Sodium influx to depolarize cell

(no other sperm can come in)

What is the slow block to polyspermy?

Intracellular calcium is released from SER to activate lysosomes to start to breakdown the zona pellucida and zona radiata