Day 11.1 Repro Flashcards
Innervation of male sex response
Erection- pelvic nerve (PNS)
Emission- hypogastric nerve (SNS)
Ejaculation- pudendal nerve (Visceral and somatic nerves)
What PNS substances are proerectile and antierectile?
NO –> increased cGMP –> smooth musc relaxation –> vasodilation –> proerectile
NE –> increased intracellular Ca2+ –> smooth musc contraction –> vasoconstriction –> antierectile
What is the location and fn of spermatogonia?
Spermatogonia are the germ cells.
They line the seminiferous tubules
They maintain the germ pool and produce primary spermatocytes
What is the location and fn of Sertoli cells?
Sertoli cells line the seminiferous tubules (like spermatogonia, altho Sertoli are not germ cells)
They secrete inhibin (which binds FSH)
They secrete ABP androgen-binding protein (which helps maintain levels of testosterone in the seminiferous tubule)
They produce anti-Mullerian hormone (mullarian inhibiting factor)
They support and nourish developing sermatozoa
Sertoli cells Support Sperm Synthesis
What forms the blood-testis barrier?
Tight jns bt Sertoli cells (which line the seminiferous tubules)
The blood-testis barrier helps isolate gametes from autoimmune attack.
What is the location and function of Leydig cells
Located in the interstitium
Leydig cells are endocrine cells- they secrete testosterone
The testosterone is kept in the tubules by the ABP that comes from Sertoli cells.
What are the relative levels of Inhibin B and FSH in pt w one testicle?
If only one testicle, the overall amt of Sertoli cells lining the seminiferous tubules will be greatly reduced. Less Sertoli means less inhibin B is made. And since there is not as much neg fdbk from inhibin on FSH production, FSH will be high.
What is the composition of semen?
60% seminal vesicle products (fructose, ascorbic acid, prostaglandins (which cause uterine contractions), phosphorylcholine, flavins)
20% Prostate products (zinc, citric acid, phospholipids, acid phosphotase, fibrinolysin)
Sperm
So if vasectomy, will still have sem fluid, just no sperm in it.
When does spermatogenesis being, how long does it last?
Starts in puberty
Full devt of sperm takes 2 months
Where does spermatogenesis take place?
Seminiferous tubules
What is the product of spermatogenesis?
Spermatids (Haploid, N) that undergo spermiogenesis- loss of cytoplasm, gain of acrosomal cap- to form mature spermatozoan.
What are the stages (with -ploid and N) of spermatogenesis?
Spermatogonium (diploid, 2N)
Primary spermatocyte (diploid, 4N)
Secondary spermatocyte (haploid, 2N)
Spermatid (haploid, N)
Spermiogenesis:
Spermatid –> Spermatozoan
How many chromosomes do spermatogonium have?
46 single chromosomes
Sex = XY
How many chromosomes do primary spermatocytes have?
46 sister chromatids
Sex = XX or YY
How many chromosomes do secondary spermatocytes have?
23 sister chromatids in each
one of the two secondary spermatocytes has X-X, the other one has Y-Y
How many chromosomes do the spermatids have?
23 single chromatids
there are 4, so the sex in 2 of them is X, and the sex in the other 2 is Y
How are Leydig cells stimulated, and what do they produce?
GnRH –> Ant Pit –> Leydig cells –> Testosterone
The testosterone feeds back to inhibit both LH and GnRH
It is kept in the seminiferous tubules by ABP, which comes from Sertoli cells
How are Sertoli cells stimulated, and what do they produce?
GnRH –> Ant Pit –> FSH –> Sertoli cells –> Inhibin and ABP
Sertoli cells support sperm production.
The inhibin feeds back to inhibit FSH.
ABP keeps testosterone (which comes from Leydig cells) around.
Mechanism of sildenafil, vardenafil, tadalafil
aka viagra
Inhibit cGMP phophodiesterase, causing increased cGMP. This causes smth musc relaxation in the corpus cavernosum, increased blood flow, and penile erection
Clinical use of sildenafil, vardenafil, tadalafil
Treatment of ED
Raynaud’s (helps vasodilate)
Primary pulm HTN
Toxicity of sildenafil, vardenafil, tadalafil
Headache, flushing, dyspepsia, impaired blue-green color vision
Risk of life-threatening hypotension in pts taking nitrates.
Hot and sweaty, but then Headache, Heartburn, Hypotension.
At what phase of spermatogenesis do the cells go thru the blood-testes barrier
When they are undergoing replication (spermatogonium –> primary spermatocytes), they pass through the tight jns bt Sertoli cells
What accumulates if Meiosis I is lost in spermatogenesis?
Primary spermatocytes (46 sister chromatids, 4N)
What accumulates if Meiosis II is lost in spermatogenesis?
Secondary spermatocytes (each of the 2 cells has 23 sister chromatids, one cell is X-X and one is Y-Y). Cells are 2N
List the androgens and where they are made
Testosterone - Testis
Dihydrotestosterone (DHT) - Testis
Androstenedione - Adrenal
Potency: DHT > Testosterone > Androstenedione
What enz converts Testosterone to DHT?
5a-reductase
What drug inhibits 5a-reductase?
Finasteride
What are the 5 functions of testosterone?
- Differentiation of epididymis, vas def, sem vesicles (all internal genitalia except prostate)
- Growth spurt (Penis, Sem Vesicles, Sperm, Muscle, RBCs)
- Deepening of voice
- Closure of epiphyseal plates (via estrogen converted from testosterone)
- Libido (in both M and F)
What are the early and late fns of DHT?
Early: differentiation of penis, scrotum, prostate
Late: prostate growth (BPH), balding, sebaceous gland activity
Where are how are testosterone and androstenedione converted to estrogen?
Converted in adipose tsu and Sertoli cells
Enz is aromatase.
What does exogenous testosterone cause wrt gonads?
Inhibits the Hypothal-Gonadal-Pit axis, which causes decreased intratesticular testosterone. This leads to decreased testicular size and to azoospermia.
Mechanism and clinical use of exog testosterone
Mech: Agonist at androgen receptors
Used to Rx hypogonadism and promote devt of secondary sex characteristics
Stim’s anabolism to promote recovery after burn or injury
Treats ER-positive breast cancer (Exemestane)
Toxicity of exog testosterone
Causes masculinization in females
Reduces intratesticular testosterone in males by inhibiting rls of LH (via neg fdbk), leading to gonadal atrophy
Premature closing of epiphyseal plates
Bad for lipids: increased LDL and decreases HDL
BPH
Benign prostatic hyperPLASIA.
Common in men >50yo
May be d/t age-related increase in estradiol w possible sensitization of the prostate to the growth-promoting effects of DHT.
Nodular enlgmt of the periurethral (lateral and middle) lobes, which compress urethra into a vertical slit. Not pre-malignant.
Increased free PSA.
Px of BPH
Increased freq of urination, nocturia, difficulty starting and stopping stream of urine, dysuria. Can lead to distention and hypertrophy of the bladder, hydronephrosis, and UTIs.
Rx for BPH
a1 antagonists (terazosin, tamulosin)- these cause relaxation of smth muscle, but do not change size of prostate
Finasteride (5a-reductase inhibitor) does decrease it.
List the anti-androgens
Finasteride (propecia)
Flutamide
Ketoconazole
Spironolactone
How does finasteride work?
Testosterone is converted to the more potent form DHT by 5a-reductase. Finasteride is a 5a-reductase inhibitor, so it decreases this conversion.
Useful in BPH, since DHT causes prostate enlargement later in life.
Since DHT also causes baldness, finasteride (propecia) can also be used to promote hair growth for pts w male patterb baldness.
Can cause impotence, gynecomastia
What is flutamide?
non-steroidal competitive inhibitor of androgens at the testosterone receptor.
Used in prostate carcinoma.
What anti-androgenic effects do ketoconazole and spironolactone have?
Ketoconazole- inhibits steroid synthesis (inhib’s desmolase)
Spironolactone - inhibs steroid binding.
Both are used to treat the hirsutism of PCOS; both have side effects of gynecomastia and amenorrhea.
Tamsulosin
a1-antagonist used to treat BPH bc it inhibits smooth musc contraction.
Selective for a1-A,D receptors, which are in urethral smooth musc
(So does not affect the a1-B receptors, which are vascular- so it does not have an effect on the BP)
Prostatic adenocarcinoma
Common in men >50
In posterior lobe (peripheral zone) of the prostate
Most freq dx’s by digital rectal exam- feel hard nodule, and prostate biopsy
PAP and PSA are useful tumor markers (PAP is prostatic acid phosphatase)
Osteoblastic mets to bone may devp in later stgs- get lower back pain and incrsd serum alk phos and PSA
Rx for prostatic adenocarcinoma
Flutamide
Resection of prostate
What happens to the PSA level in prostatic adenocarcinoma
Increased total PSA
Decreased(!) fraction of free PSA
Child w testicular and parotid gland swelling
Mumps
Cryptorchidism
Undescended testis (one or both)
Lack of spermatogenesis d/t increased body temp.
A/w increased risk of germ cell tumors
Prematurity increases risk of cryptorchidism.
Rx: Orchioplexy
Testicular torsion
Twisting of spermatic cord –>ischemia
Dx w US, but also: supporting testes gives no relief (vs epididymis, which it does give relief)
Rx: Surgical detorsion w bilateral orchioplexy w/in 6 hrs (or will have perm dmg)
Epididymitis
Inflam of epididymis
Dx: support of testes gives relief
If 35 or hx of anal, prob enterobacteriaceae (UTI bugs)- Rx is fluroquinolone
What is orchioplexy?
Suture testes to scrotum
Done for cryptorchidism, testicular torsion
Prostatitis
Inflam of prostate, px’g w dysuria, freq, urgency, low back pain. (like a UTI)
If acute and 35yo: UTI bugs- e coli, kleb, proteus, enterobacter, serratus
If chronic can be abacterial (most common) or bacterial (UTI bugs)
Rx fluroquinolones, TMP-SMX for one month!
List the testicular germ cell tumors
95% of all tumors are germ cell! they can be: Seminoma Embroyonal carcinoma Endodermal sinus (yolk sac) tumor Choriocarcinoma Teratoma
List the testicular non-germ cell tumors
5% of all testicular tumors, mostly benign
Leydig cell tumor
Sertoli cell tumor
Testicular lymphoma
Seminoma
Testicular germ cell tumor. Malignant Painless, homogenous testicular enlgmt Most common testicular tumor 15-35yo Lg cells in lobules w watery cytoplasm and fried egg appearance. Radiosensitive Late mets, excellent pgx.
Embryonal carcinoma
Testicular germ cell tumor Malignant Painful Worse pgx than seminoma Glandular/papillary morphology. Can differentiate to other tumors May be a/w increased AFP, hCG
Endodermal sinus/Yolk sac tumor
Testicular germ cell tumor Yellow, mucinous Analagous to ovarian yolk sac tumor Schiller-duval bodies resemble primitive glomeruli Increased AFP
Choriocarcinoma
Testicular germ cell tumor Malignant Increased B-hCG. Disordered synctiotrophoblastic and cytotrophoblastic elements. Hematogenous mets.
Teratoma
Testicular germ cell tumor
Mature teratoma in males is often malignant (vs benign in females)
Leydig cell tumor
Testicular, non-germ cell tumor
Contains Reinke crystals
Usu androgen producing (excess testosterone)- causes gynecomastia in men (bc of periph conversion of testosterone to estrogen), precocious puberty in boys
Golden brown color
Sertoli cell tumor
Testicular, non-germ cell tumor
Androblastoma from sex cord stroma
Testicular lymphoma
Testicular non-germ cell
Most common testicular cancer in older men.
Testicular cancer in young men? In old men? In young children up to 3yo?
Young men (15-35): Seminoma Old men: Testicular lymphoma Up to 3yo: Yolk sac tumor (endodermal sinus)
What is the female equivalent of a seminoma?
Ovarian dysgerminoma
What other tumors are similar to seminomas in appearance?
Seminoma has a fried egg appearance, similar to koilocytes of HPV and oligodendrogliomas (adult primary brain tumor)
Testicular tumor md of cytotrophoblasts and syncytiotrophoblasts
Choriocarcinoma
Testicular tumor that px’s w gynecomastia initially
Leydig cell tumor
Testicular tumor w elevated AFP
Yolk sac tumor
Embryonal carcinoma
Testicular tumor w elevated hCG
Choriocarcinoma
Embryonal carcinoma
Testicular tumor w cytoplasmic clearing (similar appearance to koilocytes
Seminoma
Testicular tumor that can have alveolar or tubular appearance, sometimes w papillary convolutions (on histo)
Embryonal carcinoma
Testicular tumor composed of multiple tsu types
Teratoma
Testicular tumor w histological endodermal sinus structures (Schiller-Duval bodies)
Yolk sac tumor
25% of this kind of testicular tumors have cytoplasmic rod-shaped crystalloids of Reinke
Leydig cell tumor
Testicular tumor that makes androgen and is a/w precocious puberty
Leydig cell tumor
Man w BPH undergoing treatment, has increased testosterone, decreased DHT, gynecomastia and edema. What’s his med?
5a-reductase inhibitor (finasteride)
Tunica vaginalis lesions
Lesions in the serous covering of testis- px as testicular masses that can be transilluminated (vs testicular tumors, which can’t be).
- Varicocele- dilated vein in pampiniform plexus; a/w infertility. “bag of worms”
- Hydrocele- increased fluid secondary to incomplete fusion of processus vaginalis
- Spermatocele- dilated epididymal duct
List the possible pathologies of the penis
Carcinoma in situ (Bowen's, Queyrat, Bowenoid) Sq Cell Carcinoma Peyronie's dz Balanitis Priapism
Bowen’s dz
Carcinoma in situ of the penis Gray, solitary, crusty plaque Usu on shaft of penis or on scrotum Peak incidence in 50-60yo Progressive to invasive SCC in <10%
Bowenoid papulosis
Carcinoma in situ of the penis
Multiple papular lesions
affects younger age group than other penile cancers
Usu does not become invasive
Erythroplasia of Queyrat
Carcinoma in situ of the penis
Red velvety plaques
Usu involves glands
Other than location, similar to Bowen’s- peak incidence at 50-60
Sq Cell Carcinoma of the penis
Commonly assoc w HPV, lack of circumcision
More common in Asia, Africa, S America
Peyronie’s dz
Bent penis d/y acquired fibrous tsu formation
T/F Bowen’s dz is a carcinoma of both men and women
True
Usu on shaft of penis or on scrotum, but can also be on female genitalia
Types of HPV a/w SCC
16, 18, 31
Balanitis
Infection of foreskin
Often fungal; 40% candidiasis
Rx: topical antifungal or 1 dose fluconazole
Priapism
Persistent penile erection Caused by: Trazodone (anti-depressant med) Sickle cell dz Trauma to the spinal cord
