Reproductive Systems (L25)

hormonal control of male reproduction

hypothalamus releases GnRH --> AP --> stimulates the secretion of FSH and LH

What does FSH bind to and stimulate the production of?

-FSH receptors in Sertoli cells

-stimulates the production of anti-mullerian hormone, inhibin, activin, and estradiol

What does LH bind to and stimulate the production of?

-surface LH receptors in Leydig cells

-stimulates the production of androgen (testosterone, dihydrotestosterone, and dehydroepiandrosterone)

3 distinct regions of the prostate

-central zone (CZ)

-peripheral zone (PZ)

-transition zone (TZ)

Where does most hyperplasia occur?

in the inner TZ, it causes urinary obstruction

Where do most carcinomas occur?

in the PZ

prostate glands

-flat basal cell and overlying columnar secretory cell layers

-surrounded by prostatic stroma

benign prostate hyperplasia (BPH)

-non-cancerous enlargement of the prostate in the inner TZ

-common in men above 50

-prostate volume > 30 mL, prostate-specific antigen 1.4 ng/mL

BPH regulation mechanism

-excessive androgen-dependent growth of stromal and glandular epithelial cells

-testosterone binds to AR and induces growth factors

-testosterone is converted to DHT by 5α-reductase, type 2

-treatment: surgically removed or the use of alpha-blockers

erectile dysfunction

-the failure to achieve or maintain a rigid penile erection suitable for satisfactory sexual intercourse

-common in men above 40

-can be psychological (depression, anxiety) or organic (hormone, neurological, traumatic, cardiovascular, age)

erectile dysfunction mechanism

-signals from the hypothalamus travel to parasympathetic nerves and cavernosal nerve to release NO to initiate the erection

-NO enters smooth muscle cells and stimulates the production of cGMP

-cGMP opens potassium channels and closes calcium channels

-low calcium causes the smooth muscle to relax and increases arterial flow

-PDE-5 degrades cGMP, causing the smooth muscle to contract and reverse to flaccid state

Why are PDE-5 inhibitors used to treat erectile dysfunction?

PDE-5 does not initiate the erection; sexual stimulation is required to release NO from the penile nerve and for endothelial cells to commence the erectile process

erectile dysfunction and coronary artery disease

-coronary arteries and the penile cavernosal arteries are similar in size and develop atherosclerosis similarly

-young men with unexplained ED have a 50-fold risk of CAD

path of ovarian follicle development

primordial --> primary --> secondary --> early tertiary/antral --> dominant/preovulatory follicle

28-day menstrual cycle

-ovarian cycle: follicular phase, ovulation, and luteal phase

-uterine cycle: menses, proliferative phase, and secretory phase

-highly controlled by GnRH, FSH, LH, estradiol, and progesterone

-3-7 days of menses or menstruation

Two-Cell, Two-Gonadotropin Concept

1. LH stimulates theca cells to make androgens that travel to the granulosa cells

2. FSH converts androgens into estrogen

menstrual cycle sequence

menstruation --> follicular growth stimulated by FSH --> ovulation (LH surge) --> luteal phase

menopause

normal condition involving the permanent end of menstrual cycles due to the cessation of the production of reproductive hormones from the ovaries for at least 12 consecutive months

menopause symptoms

-infertility

-low estrogen

-low progesterone

-high FSH

-no LH surge

-low AMH

-increased risk of osteoporosis and cardiovascular disease

hormone replacement therapy (HRT) for menopause

estrogen, estrogen-progesterone combination, or progestin

contraception

-combined oral contraception pill (COC) inhibited gonadotropin secretion --> no mature follicle --> no ovulation

-progesterone-only pill

How do estrogen components in contraception control menstrual bleeding?

they cause heavy bleeding because they interfere with the natural process

emergency contraception

-ulipristal acetate (UPA)

-levonorgestrel (LBG): progesterone agonist

-copper-bearing intrauterine device (IUD)

primary ovarian insufficiency (POI)

-amenorrhea or menopause before 40

-associated with post-menopausal syndrome, endocrine disorders, infertility, and systemic defects

-caused by genetic mutations, cancer treatments, and environmental exposures

lab results of POI

-low estrogen

-low AMH

-low LH/absence of LH surge

-high FSH

-less than 1000 primordial follicles

menopause vs POI

similar symptoms and lab results but differ in age

fragile X syndrome (FXR)

-mutation of the FMR1 gene (X chromosome)

-causes abnormal brain development, intellectual disabilities, and POI/associated reproductive dysfunctions

polycystic ovarian syndrome (PCOS) symptoms

-hyperandrogenism

-anovulation

-polycystic ovary

-infertility, irregular periods, obesity, diabetes

PCOS etiology

-unknown

-defective HPG control

-genetic mechanisms

-luteinized or hyperplasia of theca cells

-environmental exposure (gestational exposure to high androgen)

PCOS pathophysiology

-ovarian stimulation for infertility

-metformin for hyperinsulinemia

-oral contraceptive for irregular menstrual cycles

-exercise, healthy diet, body weight control

-anti-androgens

endometriosis

-presence of endometrial tissues outside of the uterus

-most common in 30-40 year old women

-release of proinflammatory of angiogenic factors

clinical consequences of endometriosis

-infertility

-dysmenorrhea

-painful menstruation

-pelvic pain

3 endometriosis pathogenesis theories

1. from the uterine endometrium - retrograde menstruation or via blood vessels

2. transformation of peritoneal cells

3. from stem or progenitor cells

treatment of endometriosis

hormones (aromatase inhibitors), surgery, pain killers