Endocrinology Exam 3 Study Guide PDF

Endocrinology Exam 3 Study Guide Hormone Control of Growth Growth Hormone (GH) Structure and Characteristics of GH 1.​ 191 Amino acid peptide hormone 2.​ Molecular weight ~22kDA 3.​ Similar structure to: prolactin and chorionic somatomammotropin (placental hormone Two isoforms of...

Endocrinology Exam 3 Study Guide Hormone Control of Growth Growth Hormone (GH) Structure and Characteristics of GH 1.​ 191 Amino acid peptide hormone 2.​ Molecular weight ~22kDA 3.​ Similar structure to: prolactin and chorionic somatomammotropin (placental hormone Two isoforms of GH: -​ Produced by alternative splicing -​ Most include all 5 exons translated to 191 aa protein of 22kD -​ 10-15% derived from smaller mRNA with omission of first secion of exon III Production and release of GH: -​ GH Produced by somatotrophs in the anterior pituitary gland -​ GH released in pulsatile bursts throughout the day → release mostly occurs at night (deep sleep associated) → GH release increases during exercise and trauma Factors influencing GH release: 1.​ Nutritional status 2.​ Metabolic conditions 3.​ Age-related sex steroids 4.​ Adrenal glucocorticoids 5.​ Thyroid hormones 6.​ Renal function 7.​ Hepatic function Circulation of GH Blood levels and binding -​ Normal circulating level: 80% of testicular mass -​ Contains a basement membrane and two cell types -​ 1. Spermatogonia: sperm-forming cells (germ cells) -​ 2. Sustentacular cells/sertoli cells: support sperm production → production of testicular fluid Sustentacular Cells Aka: nurse cells or sertoli cells: surrounds spermatogenic cells to provide support Function of Sustentacular Cells -​ Forms blood-testis barrier → prevents immune system cells in the bloodstream from deteecting newly formed antigens on sperm cells → Spermatogonia and sustentacular cells are “self” cells -​ Provides structural support for stem cell development -​ Secretes testicular fluid that helps transport sperm in seminiferous tubule -​ Provides nutrients for dividing cells -​ Produces androgen-binding protein (ABP) and inhibin, which helps regulate spermatogenesis -​ Phagoctizes damaged spermatogenic cells and excess cytoplasm released from maturing spermatids Leydig Cells Interstitial cells (Leydig cells) - found between seminiferous tubules in connective tissue. -​ Produces and secretes androgens, primarily testosterone, into surrounding interstitial fluid -​ Myoid cells = muscle-like cells that surround seminiferous tubules, contract to push sperm and testicular fluid through tubules Sperm Flow -​ Starts in seminiferous tubule -​ Goes to single straight tubule (tubuli recti) -​ Then rete testis -​ Ends in efferent ductules (ductuli efferentes) Duct System Transports sperm and is involved in ejaculation. Ejaculation: process that semen is expelled from penis. Semen: secretions from accessory structures. Provides nourishment and support to the sperm. Includes: -​ Epididymis -​ Ductus deferens (vas deferens) -​ Ejaculatory duct -​ Urethra Common role of all: movement of spermatozoa and fluid reabsorption Epididymis -​ Filled with many long, coiled tubes → site of sperm maturation and storage → phagocytosis of aging sperm → H+ secretion and acidification of fluid Regions of Epididymis : -​ head -​ body -​ tail Sperm flow: -​ → efferent ductules -​ → Ductus epididymis (head) -​ → ductus epididymis (body) -​ → ductus epididymis (tail) -​ → ductus deferens Ductus Deferens (Vas Deferens) Begins at tail of epididymis where the ductus epididymis widens: -​ Posterior border of epididymis → inside spermatic cord with testicular arteries, veins, and nerves → through a fibrous tunnel (inguinal canal) → pelvic cavity → lateral side of bladder → over ureter → posterior surface of bladder → terminates in ampulla → ejaculatory duct Ductus deferens can store sperm for months and resorb any sperm that has not been ejaculated over time Ejaculatory Duct Short duct -​ Begins at junction of ductus deferens ampulla with seminal vesicles (accessory gland) -​ Travels through prostate (another accessory gland) -​ Goes to prostatic urethra Urethra -​ Belongs to both reproductive and urinary systems. -​ Surrounded by smooth muscle to aid with ejaculation -​ Urethral mucosa: → contains several small, mucus secreting urethral glands → empties into the urethra and contributes to semen Urethra transports both urine and semen through 4 parts: 1.​ Intramural (preprostatic) - 1 cm long - surrounded by internal urethral sphincter 2.​ Prostatic urethra - 3 cm long - widest and most dilated part 3.​ Membranous urethra (intermediate) - bulbourethral glands (cowper’s glands) - 1-2 cm long - on pelvic floor - surrounded by external urethral sphincter 4.​ Spongy (cavernous or penile) urethra - bulbourethral duct opens here - 15 cm long - starts near Cowper’s gland opening - extends through penis and terminates at external urethral orifice The Penis Features that deliver sperm into female reproductive tract: 1.​ External penis - root, body, glans penis → prepuce 2.​ Internal penis - 3 bodies surrounded by buck’s fascia (dense fibrous CT) → 2 corpora cavernosa → 1 corpus spongiosum: expands to form bulb and glans 3.​ Blood supply - internal iliac arteries provide branches → internal pudendal arteries (supply blood to penis) → goes to dorsal and deep arteries - inferior epigastric artery → cremasteric branch - femoral artery → superficial external pudendal, deep external pudendal arteries 4.​ Deep dorsal vein of penis → to prostatic venous plexus 5.​ Lymphatic drainage → to inguinal lymph nodes Accessory Sex Glands Exocrine glands that produce liquid portion of semen: 1.​ Seminal vesicles: -​ influenced by androgens -​ Secretes and stores yellowish mucoid until ejaculation → makes up 60-70% of semen volume -​ secretion composed of: → fructose: sugar for ATP synthesis → prostaglandins: stimulates smooth muscle contraction in both gender’s reproductive tract. Increases sperm viability → Coagulating proteins and enzymes: to form a temporary clot of semen in female reproductive tract 2.​ Prostate gland-milky fluid: -​ Egg sized gland found inferior to urinary bladder -​ Surrounds urethra and ejaculatory ducts -​ influenced by androgens -​ Makes up 20-30% of semen volume: 3.​ Bulbourethral glands: -​ Aka: Cowper’s gland -​ Marble - sized paired glands -​ Found at base of penis  -​ Secrete a thick, alkaline mucus - like fluid → helps neutralize acidic urine remaining in urethra -​ Lubricates glans penis during intercourse Semen Somewhat sticky whitish mixture Includes: sperm and all fluids from different anatomicals structures sperm traveled through. -​ Sperm contributes ~10% of semen’s total volume -​ Typical ejaculate is between 2.5 and 5 ml in volume → 40-750 million sperm cells Summary of Male Reproductive System 1.​ Seminal Vesicles 2.​ Prostate 3.​ Cowper Glands 4.​ Epididymis 5.​ Sertoli (epithelial cells) 6.​ Leydig Cells Gonadotropin Regulation of Gonadal Function Follicle Stimulating Hormone (FSH) Characteristics: -​ Half - life: 1-3 hours -​ Stable plasma levels -​ Less variability Signal transduction: -​ Hormone binding to membrane receptors (GPCR) -​ Located on Sertoli cells -​ Intracellular cascade Functions: -​ Controls Sertoli proliferation -​ Regulates seminiferous tube growth -​ Determines testicular size: → Normal adult dimensions: 4.1- 5.2 cm length, 2.5 - 3.3 cm width -​ Initiates spermatogenesis at puberty -​ Promotes androgen-binding protein production -​ Develops blood-testis barrier Luteinizing Hormone (LH) Characteristics: -​ Half-life: 30 mins -​ Higher amplitude fluctuations -​ More variable levels Primary Function: -​ Regulates testosterone production by Leydig cells Signal Transduction: -​ Hormone binding to membrane receptors (GPCR) -​ Located on Leydig cells -​ Intracellular cascade Control of Gonadotropin Synthesis and Release GnRH pulse generator -​ Stimulatory signals → Norepinephrine → Serotonin (5-HT) → Neuropeptide Y (NPY) -​ Inhibitory Signals → 𝛽 - endorphin → GABA → Dopamine → Interleukin 1 -​ Dual action → 17𝛽 - estradiol (both stimulatory and inhibitory) GnRH Signaling Pathway -​ GnRH binds to GPCR -​ + phospholipase C activation -​ Leads to increase in inositol trisphosphate (+) and diacylglycerol (DAG) -​ Increases protein kinase C -​ Increases cytosolic Ca2+ -​ Gonadotropin is released Pulse frequency effects -​ FSH production → highest with low-frequency GnRH pulses → 𝛽 - subunit synthesis decreases with higher frequency -​ LH production → Enhanced by higher frequency GnRH pulses → higher amplitude stimulates 𝛽 - subunit synthesis Testosterone feedback loop -​ Testosterone inhibits: → GnRH release (hypothalamic level) → Gonadotropin 𝛽 - subunit synthesis (pituitary level) → LH pulse amplitude and levels -​ Key points: → Most testosterone effects mediated by 17 𝛽 - estradiol (local metabolite) FSH feedback loop -​ Inhibin B (from Sertoli cells) → Primary negative feedback at pituitary level → Controls FSH release Inhibin and Activin: Local Regulators of Gonadotropins Inhibin B -​ Characteristics: → member of TGF - 𝛽 superfamily → produced by Sertoli cells → FSH - dependent production -​ Function: → Negative feedback on FSH → Specifically inhibits: FSH 𝛽 - subunit production and FSH release Activin -​ Characteristics: → Multi-tissue expression (including pituitary) → TGF - 𝛽 family member -​ Function: → Antagonized inhibin B → Stimulates FSH release Gonadal Hormone Synthesis & Metabolism: Testosterone LH → Leydig cells → testosterone LH’s mechanism -​ Rapid response (minutes) → increase in cholesterol mobilization → enhanced transport into steroidogenic pathway -​ Slower response (hours) → (+) gene expression → increased STAR and P450scc activity Key steps in testosterone biosynthesis -​ Resembles adrenal androgen synthesis 1. Cholesterol transport → STAR protein facilitates movement into mitochondria 2. Sequential enzymatic conversions → Unique to teste: androstenedione to testosterone (uses 17𝛽 - hydroxysteroid dehydrogenase Plasma Protein Binding -​ Testosterone primarily bound to: → SHBG (44%) - High affinity and specificity → Albumin (54%) - Low affinity, limited specificity -​ Only small fraction exists as “free” hormone -​ Binding proteins act as “primary gatekeepers” of hormone action Sex Hormone-Binding Globulin (SHBG) -​ Produced in liver -​ Also expressed in: → brain → placenta → testes -​ Involved in non-genomic steroid signaling -​ Functions independently of cytosolic androgen receptor Testosterone binds to Androgen-Binding Protein (ABP) -​ ABP produced by Sertoli cells -​ Released into seminiferous tubules -​ Transports testosterone -​ Structurally similar to SHBG Testosterone effects, two main pathways: 1.​ Direct effect through androgen receptor 2.​ Metabolic conversion to: - 17𝛽-estradiol (via aromatase) - 5𝛼-dihydrotestosterone (DHT) (via 5𝛼 - reductase) → Enzymatic conversion is irreversible Gonadal Hormone Synthesis: Estradiol -​ Converted from testosterone by aromatase enzyme -​ Aromatase found in: → Leydig cells → adipose tissue → brain → bone -​ Testicular production contributes ~20% of circulating estrogen in males -​ Epiphyseal growth & closure -​ Negative feedback: GnRH Androgen Receptor-Mediated Physiologic Effects Androgen receptor structure and function -​ Member of nuclear receptor superfamily -​ Three functional domains involved: -​ → Transcriptional regulation -​ → DNA binding -​ → Ligand binding -​ Both testosterone and DHT bind to same receptor Testosterone-specific effects: -​ Sexual differentiation -​ Libido -​ Pubertal larynx growth -​ Deepening of voice -​ Muscle anabolic effects and RBC -​ Spermatogenesis stimulation -​ Negative feedback: GnRH, LH, FSH DHT - specific effects: -​ Most potent androgen receptor activator -​ Longer half-life than testosterone -​ Primary roles: → Embryonic external virilization → Male external genitalia development → prostate development → Facial/body hair growth → male pattern baldness (in genetically predisposed) -​ Mainly intracrine effects (at 5𝛼-reductase expressing cells) -​ Small amount (~10% of testosterone level) enters circulation Functions of Hormones During Fetal Development 1.​ Development of male genitalia during female development 2.​ Descent of testes 3.​ Sexual differentiation process in humans -​ Controlled by genetic and hormonal factors -​ Y chromosome triggers: → Sertoli cell differentiation → Spermatogonia development → Testis formation Key hormones and effects: 1.​ Mullerian inhibitory factor (MIF/MIS/AMH): - secreted by Sertoli cells - Causes Mullerian duct regression 2.​ Testosterone: - Secreted by Leydig cells → hCG (from placenta) initiates Leydig cell activation → Later controlled by LH - Develop Wolffian duct structures - Increases androgen receptor expression 3.​ DHT: - Promotes prostate/penis growth Sex determination: 3 sequential processes 1.​ Genetic Sex: - determined at fertilization - X or Y sperm determines sex - Normal male: 46, XY 2.​ Gonadal Sex: - Controlled by Y chromosome genes - SRY gene crucial role: → produces testis determining factor (TDF) → TDF initiates male development, absence → ovarian development → converts bipotential cells to Sertoli cells 3. Phenotypic Sex: - Development of internal/external genitalia - Driven by hormones from developed gonads Testicular Descent (finalizes sexual differentiation) -​ Two step process: 1. Transabdominal migration 2. Descent into scrotal sac -​ Controlled by: → Testosterone → INSL3 (insulin peptide/factor 3) aka: Leydig insulin like hormone or relaxin-like factor Effects of Androgens on Other Body Systems Puberty overview: -​ Begins age 12-14 -​ Lasts about 4 years -​ Triggers increase in pulsatile GnRH secretion → stimulates activation of HPG axis -​ Increases growth hormone (GH) secretion Increase in testosterone levels triggers: -​ Increase in gonadotropins leads to testicular enlargement → LH increases sleep initially → LH later becomes constant throughout the day -​ Increase in sex steroids leads to activation of spermatogenesis -​ Increased conversion to DHT by 5𝛼-reductase leads to growth of prostate/seminal vesicles/epididymis -​ Appearance of secondary sexual characteristics Once spermatogenesis begins, males are capable of sexual reproduction Secondary sexual characteristics: -​ First develops primarily at puberty and continues through early adulthood -​ Changes include: → growth of facial/body hair → Pubic hair growth → Enlarged larynx and thick vocal cords (voice deepening) → Thickened skin → Increase secretion of sebaceous glands → Penis enlargement Testosterone causes somatic effects anabolic in nature: -​ Increased bone density → due to greater amount of calcium salts deposited -​ Increase in skeletal muscle mass -​ Increase in erythrocyte production → increase in testosterone causes increase in erythropoietin secretion Testosterone influences behaviour -​ Basis for male libido (desire for sexual activity) Spermatogenesis The continuous process of germ cell differentiation to produce spermatozoa How is spermatogenesis regulated: -​ By hormones from hypothalamus and anterior pituitary gland -​ → GnRH stimulates more FSH than LH, leads to Spermatogenesis Spermatogenesis begins: -​ At puberty (continues for life) -​ → healthy young adult male makes ~400 million sperm/day Spermatogenesis occurs: -​ In seminiferous tubules -​ → done by sperm forming (spermatogenic) cells in blood testes barrier Proliferation: -​ Spermatogonia → primary spermatocytes -​ Mitotic divisions maintains stem cell pool -​ → 46 chromosomes (diploid, 2n) -​ Some cells are dormant, others differentiate -​ → Before puberty: → divides only by mitosis → 2 stem cells -​ → After puberty: → functional stem cells divide by mitosis → 1 stem cell + 1 primary spermatocyte Meiosis in Spermatogenesis: -​ Primary spermatogenesis undergoes two divisions -​ Produces secondary spermatocytes, then spermatids -​ Results in haploid cells (23 chromosomes) Spermiogenesis: Process of sperm maturation -​ Involves cellular shape and size changes: -​ → Nuclear condensation -​ → acrosome formation -​ → tail development -​ → mitochondrial organization -​ → cytoplasm reduction Spermiation -​ Release of mature sperm from sertoli cells -​ Sperm enters tubule lumen Spermatocytogenesis → Spermiogenesis → Spermiation (lasts 60-70 days)