Term
| What are the three divisions of male reproduction? |
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Definition
- Spermatogenesis
- Sexual function
- Regulation of functions by hormones |
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Term
| What are the components of the male reproductive system? |
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Definition
- Testis - major male machinery. Composed of coiled seminiferous tubules. Empties into epididymis
- Epididymis very long, stores sperm. Tail empties into vas deferens
- Vas deferens - smooth muscle responsible for ejaculation. Goes to prostate gland and urethra. |
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Term
| What are the 2 layers of the testes? |
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Definition
- tunica vaginalis - outer capsule
- tunica albuginea - inner fibrous capsule
- septa divide testis into ~250 lobules. Each lobule contains the seminiferous tubules
- Tubules converge --> straight tubule to direct sperm to rete testis.
- Leaves via efferent ductules --> epididymis |
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Term
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Definition
| Through the epididymis, not the testes |
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Term
| When and where does spermatogenesis occur? |
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Definition
| In the seminiferous tubules during active sexual life. Stimulation by anterior pituitary - LH/FSH |
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Term
| What is the first stage of spermatogenesis? |
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Definition
| Spermatogonia (germ cells) migrate while being nourished by Sertoli cells, undergo mitosis --> primary spermatocyte. Miosis --> secondary spermatocyte. Starts to undergo Miosis 2 but does not finish -- finishes upon fertilization --> spermatid --> spermatozoa. 23 pairs of chromosomes. |
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Term
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Definition
- Acrosome - proteolytic enzymes used to penetrate the egg
- Tail - microtubules (axoneme) and mitochondria
- moves faster in semen, slower in acid (vagina)
- Body temperature affects sperm production - scrotum controls |
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Term
| How do hormones control spermatogenesis? |
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Definition
- LH - control the leydig cells, involved in synthesis and release of testosterone. Testosterone --> Sertoli cells to support spermatogenesis
- Sertoli cells also make some testosterone and convert to estrogen. FSH has a positive effect on Sertoli cells
- Inhibin - comes from sertoli cells, has negative feedback on hypothalamus and anterior pituitary
- GnRH - produce LH/FSH. In it's absence, testis atrophy and testosterone/sperm production stops. |
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Term
| What hormones are critical to spermatogenesis? |
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Definition
- GnRH - induces release of LH/FSH
- Testosterone - Secreted by Leydig cells. Needed for spermatogonia
- LH - Stimulates Leydig cells to secrete testosterone
- FSH - Stimulates sertoli cells to convert spermatids to sperm
- Estrogens - formed by Sertoli cells, necessary for spermatogenesis
- hGH - controls metabolism of testes, w/o = infertility
- Inhibin - released from Sertoli cells, negative feedback on GnRH and FSH |
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Term
| What are anabolic and androgenic effects of testosterone? |
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Definition
Anabolic - increased muscle and tissue mass, bone density
Androgenic - growth of penis, scrotum, testes. Hair growth, prostate growth, skin thickening. |
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Term
| What are metabolites of testosterone? |
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Definition
- DHT - converted by 5alpha-reductase, removing 4-5 double bond. Also acts on androgen receptor
- Estradiol - converted by aromatase. Acts on estrogen receptor |
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Term
| What is Wolfian development? |
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Definition
| During gestation, caused by testosterone binding to the androgen receptor. Internal genitalia development |
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Term
| What do high levels of DHT/low testosterone lead to? |
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Definition
| Male pattern baldness, BPH, prostate cancer |
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Term
| What is the only stage in life where testosterone is not maintained? |
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Definition
Childhood.
gestation and infancy, testosterone is high to differentiate
Gradual decline later in adulthood (senescence) - decreased energy and libido. |
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Term
| Where is sperm stored and for how long? |
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Definition
In the vas deferens, for up to 1 month. Sperm is continually made, up to 120 million/day. Maturation and motility happens after ejaculation.
- Both sertoli and epididymis necessary for sperm maturation. |
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Term
What is the function of the prostate gland?
Seminal vesicles? |
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Definition
- Secretes a milky basic fluid upon contraction of the vas deferens, neutralizing acid in the vas deferens AND the vagina
- Allows sperm to be more motile in a more basic environment
---------
- Seminal vesicles lined w/ secretory cells, high levels of fructose and prostaglandins. 60% along w/ sperm and prostate gland fluid.
- Prostaglandins aid in fertilization by helping move the sperm up into the cervix |
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Term
| What are the characteristics of semen? |
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Definition
All the fluids:
Semen (2-5%), vas deferens (10%), prostatic fluid (30%), seminal vesicle fluid (60%)
Slightly alkaline, pH 7.5. Has clotting factors - coagulates upon ejaculation. Dissolves over a 15-30 min period and sperm become motile, can live for 24-48 hours in the vagina. |
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Term
What is the most important source for for sensory nerve signals in the penis?
What are 2 areas inside the penis? |
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Definition
Tip of the penis/glans penis
Corpus cavernosum - two sponge pieces which hold the deep arteries
Corpus spongiosum - smaller, holds the urethra
- flaccid - both Corpi are constricted and lack blood
- Erect - Both are relaxed and fill with blood. ED: chambers cannot fill with blood. |
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Term
| How is the penis innervated? |
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Definition
- At rest/flaccid - NE/adrenergic output --> smooth muscle contraction, decr blood filling
- Erect - PNS/sacral tracts dependent on Ach and NO --> smooth muscle relaxes and incr blood filling. |
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Term
| How is penis flaccidity mediated by innervation? |
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Definition
SNS innervates SM surrounding corpus cavernosum. NE released and acts on alpha2 receptors --> Gi receptor. Decreased cAMP increases calcium and contraction of SM --> flaccidity.
NE --> alpha1 --> IP3/DAG pathway, increased calcium and phosphorylation of myosin |
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Term
| How does CNS stimulation affect the penis? |
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Definition
Stimulation prompts the release of dopamine --> INHIBITS NE release.
Ach release from sacral portions--> erection. PSNS releases NO and VIP. NO relaxes arteries of the penis
Degree of erection is proportional to degree of stimulation |
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Term
| How is the penile erection facilitated by innervation? |
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Definition
- Decr in SNS tone affects cavernous neuron --> nNOS releases NO. NO (eNOS) also released by Ach acting on M3.
- NO promotes cGMP --> K efflux and hyperpolarization. Without calcium, the tissue relaxes, allowing blood flow |
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Term
| What drugs can improve an erection? |
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Definition
- Alpha1 antagonists
- Alpha2 antagonists
- ARBs
- DA agonists
- PDE5 inhibitors |
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Term
| What is the purpose of the corpus spongiousum? |
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Definition
Surrounds the urethra, 10% of blood. Provides a buffer to keep the swelling of the corpus cavernosum from closing the urethra
**Maintain the integrity of the urethra |
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Term
| What is the purpose of the bulbourethral gland? |
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Definition
| At the base of the urethra, secretes Cowper's fluid, which lubricates the urethra for sperm passage, neutralizes urine, and can flush out old sperm. |
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Term
| What role does the spinal cord have in ejaculation? |
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Definition
Thoracic and Lumbar areas close off the bladder to the urethra (serotonin
Sacral area leads to expulsion via vas deferens into urethra
- Entry of other fluids mix in internal urethra = emission, a feeling of fullness
- Ejaculation - contraction of ischiocavernosus and bulbospongiosus muscles, wavelike increases in pressure
- Resolution - SNS inhibits erection |
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Term
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Definition
non-cancerous enlargement of the prostate gland, DHT dependent.
Occludes the urethra |
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Term
| What are the symptoms associated with BPH? |
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Definition
- Obstructive symptoms - poor stream, dribbling, large residual volume
- Irritation - urination hesitancy, increased frequency, nocturia
- Increased by Alcohol, cold, immobility, OTC sympathomimetics and anticholinergics. |
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Term
| What improves BPH symptoms? |
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Definition
| Blocking 5alpha reductase - inhibits to conversion to DHT |
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Term
| What drugs can be used to tread erectile dysfunction? |
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Definition
- PDE(5) inhibition: Paparavine, Sildenafil/Viagra, Vardenafil/Levitra, Tadalafil/Cialis
- alpha2 receptor blockade - Yohimbine
- Alpha1 blockade/vasodilation - Phentolamine
- local prostaglandin delivery - Alprostadil |
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Term
| How does blocking PDE help in erectile dysfunction? |
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Definition
PDE inhibited, cannot break down NO. Increase in cGMP --> hyperpolarization and calcium removal --> relaxation and erection
PDE5 enriched in the corpus cavernosum. |
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Term
| Why do PDE5 inhibitors cause visual disturbances? |
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Definition
Have some affinity for PDE6, which is found in the retina
Sildenafil/Viagra more likely.
PDE11 - muscle pain - tadalafil/Cialis |
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Term
| What are similarities and differences between the PDE5 inhibitors? |
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Definition
All cause hearing loss, 3A4 metabolism.
Tadalafil lasts 17 hours due to structure changes
Tissue MUST be able to generate NO to work. |
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Term
| How does Phentolamine/Rogitine work? |
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Definition
Alpha1 and 2 blocker -- vasodilation due to relaxation at SM, swelling of c. cav.
- Remember NE affecting alpha2/cAMP contracted SM, blockade leads to erection
- Remember NE --> alpha1/IP3-DAG contracted SM, blockage leads to erection
= blockade of anti-erectile fxns |
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Term
| How does Yohimbine/Yocon work? |
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Definition
Pre- and post- synaptic alpha2 antagonist
- pre-synaptic antagonism leads to greater NE release, but alpha2 is block so still get an erection.
- Used in tandem w/ phentolamine |
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Term
| What is the MoA for alprostadil/Caverject or Muse? |
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Definition
synthetic PgE1 for intercavernosal injection or intraurethral suppository --> vasodilation and relaxation via cAMP/PKA
- sometimes used w/ paparavine or phentolamine |
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Term
| What is priapism? What is the treatment? |
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Definition
Penis remains erect w/o stimulation for more than 4 hours - can cause permanent damage
Caused by ALL ED agents.
Tx: Injected phenylephrine |
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Term
| What is the hypothalamic-pituitary-reproduction axis in men? |
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Definition
Hypothalamus secretes GnRH --> anterior pituitary secretes LH/FSH --> Leydig and Sertoli cells in testes secrete testosterone
Testosterone acts on muscle development, adipose, and ducts.
Testosterone exerts negative feedback on hypothalamus and ant. pituitary. Inhibin inhibits FSH. |
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Term
| How does androgen signalling take place? |
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Definition
Testosterone circulates bound to SHBG
Unbound, crosses cell membranes and acts as testosterone or DHT on an androgen receptor
Androgen binding knocks heat-shock protein off receptor, allowing it to dimerize.
Dimers move into nucleus and make new proteins. |
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Term
| What are the consequences of androgen deficiency? |
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Definition
Depends on when it occurs;
- In utero: Complete absence = female phenotype. Mild absence = impaired spermatogenesis
- Failure to complete puberty. Gynecomastia
- after puberty: decr libido, decr energy, decr muscle mass/bone, decr Hct/Hgb |
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Term
| Why are androgens not orally bioavailable? |
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Definition
| 1st pass metabolism - rapid hepatic metabolism |
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Term
| How do injectable testosterone esters work? |
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Definition
Esterified to be lipophilic, lasts 2-4 weeks.
Levels go higher than normal, then slowly return to sub-therapeutic. Must maintain injections
Test. Enanthate/Delatestryl
Test. Cypionate/Depo-testosterone
Test. Propionate/Testex |
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Term
| What characteristics are increased by anabolic steroids/alkylated androgens? |
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Definition
Incr appetite
Incr bone and muscle growth
Stimulation of bone marrow and RBC
Incr libido, sebaceous gland activity
Androgen:anabolic effect is key. |
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Term
| Which drugs are alkylated androgens and what are their properties? |
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Definition
- Methyltestosterone/Oretin Methyl. 17-methyl, has 1:1 activity. This addition increases oral activity
- Fluoxymesterone/Halotensin - 17-methyl and 9-Fluoro yields 1:2 and:ana but has MR affinity
- Oxandrolone/Oxandrin - looks like DHT (double bond reduced). Incr anabolic, decr androgenic
- Stanozolol/Winstrol - Incr anabolic, decr androgenic
- Danazol/Danocrine - ring substitute and 17-ethinyl. Decreases LH/FSH in cancer = antigonadotrophic |
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Term
| Why would transdermal androgen be used? |
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Definition
Avoids 1st pass
Facilitates transport
MUCH more stable concentrations |
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Term
| What is the main side effect of androgen replacement therapy? |
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Definition
Suppresses endogenous testicular function --> atrophy and infertility
Risks: BPH, liver dmg, gynecomastia, increased fluid retention, oil/acne, body hair. |
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Term
| What are the sites that anti-androgen therapies act? |
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Definition
- Ketoconazole - all steroidogenesis by inhibiting SCC in the testes and elsewhere
- Spironolactone in the testes and androgen receptors
- Finasteride and dutasteride inhibit 5alpha reductase
- Flutamide and Cyproterone are androgen receptor antagonists.
- GnRH agonism |
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Term
| How do GnRH agonists work? |
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Definition
| Desensitization: downregulation of the GnRH receptor on the anterior pituitary --> decrease in entire pathway |
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Term
| What drugs are GnRH agonists? |
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Definition
- Leuprolide/Leupron
- Buserelin/Suprefact
- Nafarelin/Synarel
- Histrelin/Supprelin
- Goserelin/Zoladex
- Deslorelin/Suprelorin |
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Term
| What are 5alpha-reductase inhibitors used to treat? |
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Definition
BPH. DHT causes BPH, enzyme necessary for conversion of testosterone.
Can reverse BPH to some extent
2 isoforms: type II more selective for DHT.
- Finasteride/Proscar - more potent for type II isoform
- Dutasteride/Avodart - inhibits both isoforms.
AE: hair growth, IMPOTENCE |
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Term
| Do alpha blockers affect androgen levels? |
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Definition
NO! They simply relax prostate tissue.
-alpha1A expressed in prostate/urethra
- Antagonism = relaxation. Can be a1-antagonists or specific for alpha. |
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Term
| What drugs are alpha blockers? |
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Definition
- Prazosin/Minipress
- Terazosin/Hytrin
- Doxazosin/Cardura
- Alfuzosin/Uroxatral
- Tamsulosin/Flomax - alpha selective
- Silodosin/Rapaflo - alpha selective |
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Term
| What drugs are androgen receptor antagonists, and how do they work? |
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Definition
Pure anti-androgens: block the kicking off of the HSP from the androgen receptor, receptor can't dimerize. Used in cancers.
- Flutamide/Eulexin
- Biclutamide/Casodex
- Nilutamide/Nilandron
- Cyproterone/Androcur |
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Term
| What is the problem with androgen receptor antagonists, and how is it solved? |
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Definition
Negative feedback on the hypothalamus and anterior pituitary is loss, leading to a surge in GnRH and LH/FSH
- Fix: given with GnRH agonist |
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