Let X be a random variable with probability densityfunction (a) What is the value of c?(b) What is the cumulative distribution functionof X?
BIOL 2510 notes for test 3 Overview – anatomy Primary sex organs: gonads Male = testes Females = ovaries Produce: o Gametes (sperm and ova) o Hormones: testosterone, estrogen Secondary sexual characteristics Regulate reproductive system Accessory (secondary) reproductive organs Reproductive tract – ducts and organs o Receive, store, transfer gametes o Female: environment for development of zygote, embryo, fetus Accessory glands – fluids for transfer External genitalia – transmission of gametes Male reproductive system – testes Within scrotum Sperm 3 degrees Celsius below core body temperature (about 93.2 degrees Fahrenheit) Cremaster muscle – elevates or suspends testes o Proximity to core Dartos muscle – o Shrinks/expands scrotal skin Cold – shrink Hot – expand Seminiferous tubules – site of spermatogenesis = production of spermatozoa (sperm cells) o Spermatogenic cells – in epithelial walls of seminiferous tubules and give rise to sperm Includes spermatogonia, spermatocytes, spermatids Spermatogenesis: o Spermatogonia – stem cells divide through mitosis and become primary spermatocytes meiosis I forming secondary spermatocytes meiosis II becoming __________________________________ Seminiferous tubules 1. Spermatogenic cells: meiosis sperm 2. Sertoli cells (sustentocytes) Bloodtestis barrier Sperm are genetically unique Nutrients and signaling molecules Move spermatogenic cells along to lumen Phagocytize Defective cells and cytoplasm Secrete inhibin and androgenbinding protein (ABP) – regulate spermatogenesis 3. Leydig cells (interstitial endocrine cells) – produce testosterone 4. Myoid cells: contract, move sperm through tubule Tunics: Tunica vaginalis o “sheath” o Two layered o Derived from peritoneum Tunica albuginea o “white coat” o Fibrous capsule o Septa lobules containing Seminiferous Tubule Male reproductive system – Sperm’s big adventure Seminiferous tubules Rete testis – sperm from seminiferous tubules Efferent ductules – sperm from efferent ductule, mature and stores sperm Vas (ductus) deferens – (in spermatic cord) paired tubes that deliver sperm to ejaculatory duct Ejaculatory duct – connects vas deferens to urethra Urethra: 3 regions – prostatic, membranous, and spongy Male reproductive system – Penis Penis – copulatory organ for delivering sperm to female reproductive tract o Root – attachment to body o Shaft – body that contains erectile tissue: Corpus spongiosum – midventral erectile tissue surrounding (spongy) urethra Bulb of penis at root Corpora cavernosa – paired dorsal erectile tissue (most abundant tissue of penis) Crus of penis at root Both are dense CT, smooth muscle, and vascular spaces o Glans penis – enlarged tip of penis Prepuce – foreskin that encloses the glans Removal = circumcision (60% of newborn males in US) Male reproductive system – Accessory glands Semen – milky white mixture of sperm and accessory gland secretions Accessory glands: o Seminal vesicles (2) – alkaline fluid, 70% of semen. Enhance sperm motility and fertility Fructose citrate Coagulating enzyme (vesiculase) o Prostate gland (1) – slightly acidic fluid activates sperm, 2030% Citrate Enzymes Prostatespecific antigen o Bulbourethral glands (2) – thick, clear mucus for lubrication and to neutralize urine 1. Question: Fructose (a carbohydrate) is aerobically metabolized by sperm cells. This means that fructose functions as a(n) ________ source for the sperm. a. Energy Male reproductive system – semen Composition and purpose: o Relaxin: hormone that enhances sperm motility o Citrate (ATP) and fructose: provide energy for sperm o Prostaglandins: decrease viscosity of mucus at the cervix and stimulates sperm movement through female reproductive tract o Suppression of immune response in female reproductive tract o Antibiotics: destroy some bacteria o Clotting factors: cause coagulation to vagina wall Male reproductive system – erection and ejaculation Erection – enlargement, stiffening of penis o Parasympathetic reflex to arousal: Nitric oxide released locally – vasodilation of arterioles supplying erectile tissue and blood fills vascular spaces Expansion of corpora cavernosa compresses drainage veins (to maintain erection) Corpus spongiosum keeps urethra open during ejaculation Ejaculation – propulsion of semen from male duct system o Under sympathetic control: Bladder sphincter constricts (keeps urine and semen separate) Reproductive ducts and accessory glands contract – empties contents into urethra Spinal reflex triggers muscle contraction and semen release from urethra o Refractory period – time after ejaculation before another erection can be achieved Mitosis/meiosis review Diploid chromosomal number (2n) – normal chromosome number in most body cells; 46 in humans (23 pairs of homologous chromosomes) Haploid chromosome number (n) – number of chromosomes in gametes; 23 in humans Mitosis – process by which most body cells divide; replicated chromosomes distributed equally to 2 daughter cells o Chromosomes replicated o Chromosomes align o Sister chromatids pulled toward the opposite polls o Each daughter cell has a copy of every chromosome Meiosis I – process of nuclear division that forms the gametes; occurs in gonads o Chromosomes replicated o Synapsis – replicated chromosomes pair up with their homologue o Chromosomes align o Homologous chromosomes separated to opposite poles o Each daughter cell has haploid chromosome number Meiosis II – o Chromosomes align o Sister chromatids pulled apart 1. Question: true or false. Spermatazoa are haploid because they have gone through meiosis and have a chromosomal number of 1n. a. True 2. Spermatagonia are haploid because they have gone through meiosis and have a chromosomal number of 1. a. False – spermatoagonia are stem cells that go through mitosis and are diploid Male reproduction system – hormonal regulation The hypothalamicpituitarygonadal (HPG) axis: o Gonadotropinreleasing hormone (GnRH) from hypothalamus causes a release of: Luteinizing hormone (LH) and follicle stimulating hormone (FSH) from anterior pituitary LH causes Leydig cells secrete testosterone (T) for spermatogenesis FSH causes Sertoli cells to secrete inhibin and androgen binding protein (ABP) Negative feedback o Inhibin inhibits FSH secretion o Testosterone inhibits GnRH and LH secretion, leading to lower T levels Testosterone from Leydig cells: o Fetus Male external genitalia o Neonate Brain development, sexual differentiation, o Puberty – 2 sex characteristics: Pubic, axillary, facial, chest hair Deepening of the voice Skin thickens and becomes oily Bones grow and increase in density Skeletal muscles increase in size and mass o Is the basis of libido in both males and females DHEA important in females Male reproductive system – Pathologies 1. Cryptorchidism – “hidden” testes 2. Testicular cancer a. Most common cancer in young men b. Risk factors: orchitis and cryptorchidism c. Detection: selfexam. Solid mass. 3. Prostate ndncer a. 2 most common causes of death in men b. Risk factors: fatty diet, genetic predisposition i. Retrovirus – newly discovered, sexually transmitted enzyme in semen increases male susceptibility c. Detection: palpation, ultrasound, blood levels of PSA Read your book: pages 10541062 Female Reproductive system – ovaries 1. Ovaries – produce ovum (=egg) and secrete hormones such as estrogen and progesterone a. Layers of ovary i. Cortex – houses forming gametes ii. Medulla – large blood vessels and nerves 2. Ligaments: a. Ovarian ligament – anchors to uterus b. Suspensory ligament – anchors to pelvic wall c. Mesovarium – encloses and holds ovary in place 3. Ovarian follicles = immature egg (oocyte) and surrounding cells (follicle cells or granulosa cells) a. Oogenesis – egg production i. In fetus: oogonia – stem cells divide through mitosis and become primary oocytes start meiosis but arrested in late prophase 1 until puberty ii. After puberty: 1 primary oocyte finish meiosis 1 first polar body (smaller haploid cell) and secondary oocyte 1. Secondary oocyte begins meiosis 2 but arrested at metaphase 2 and is ovulated 2. If no sperm penetrates: oocyte deteriorates 3. If sperm penetrates: secondary oocyte finishes meiosis 2 second polar body and ovum b. Follicular development i. Primordial follicle – primary oocyte and single layer of follicle cells ii. Primary follicle – primary oocyte and single layer of enlarged follicle cells iii. Secondary follicle – primary oocyte and multiple layers of granulosa cells iv. Vesicular (antral) follicle – with large fluid filled antrum (cavity); secondary oocyte sitting on stalk of cells 1. Ovulation – single, secondary oocyte ejected from ovary into fallopian tube; once a month v. Corpus luteum – “yellow body”, ruptured follicle after ovulation. Secrete progesterone and estrogen to maintain pregnancy until placenta takes over vi. Corpus albicans – “white body”, if no pregnancy; scar left after corpus luteum regresses Female reproduction system – comparison with male 1. Female: monthly changes of a menstrual cycle a. 1 oocyte each month (male 20150 million sperm/mL ejaculation) 2. Female: all gametes they will ever have are produced at birth (probably) a. 500 oocytes ovulated (male continuous production) 3. Oogenesis 1 viable gamete (spermatogenesis 4 viable gametes) 4. Oogenesis begins in the fetus (spermatogenesis begins at puberty, ~age 14) Female reproductive system – uterine tubes Uterine (fallopian) tubes (oviducts) – receive ovulated oocyte, site of fertilization, no contact with the ovaries o ~4 inches long o Ampulla – enlarged distal end of tube where fertilization takes place o Infundibulum – funnelshaped end of tube with ciliated projections (fimbriae) that drape over ovary o Isthmus – constricted proximal region where uterine tube joins uterus o Composed of: Sheets of smooth muscle (move oocyte toward uterus) Highly folded mucosa with ciliated cells (move oocyte toward uterus) and nonciliated cells (secrete moist, nutritive fluid) Uterus – hollow, muscular organ that receives, retains, and nourishes a fertilized ovum o Anterior to rectum and posterosuperior to bladder o ~3 inches long (nonpregnant) o 3 regions: body, fundus, cervix o 3 layers of uterine wall: Perimtrium – serous layer Myometrium – smooth muscle, expels baby during childbirth Endrometrium – mucosal lining where embryo implants, sheds if no implantation occurs Vagina – thin walled tube extending from cervix to body exterior o ~34 inches long o Female organ of copulation (chamber for sperm deposition) o 3 layers of vaginal wall: adventitia, muscularis, mucosa (contains rugae) Homologous structure Shared embryonic or evolutionary origin 1. Question: ABP functions to: a. Concentrate testosterone 2. ABP is found mainly in: a. Sertolli cells Homologous structure Shared embryonic or evolutionary origin Female reproductive system – external genitalia 1. Mons pubis – rounded fatty area overlying pubic symphysis 2. Labia: a. Labia majora – lateral skin folds: homologous to scrotum b. Labia minora – medial skin folds: homologous to ventral penis 3. Vestibule – recess enclosed by labia minora that contains external urethral and vaginal orifices 4. Greater vestibular glands: mucous secreting glands on posterolateral sides of vaginal opening for lubrication: homologous to bulbourethral glands 5. Clitoris – partially protruding structure composed of erectile tissue (like corpora cavernosa); anterior to urethral orifice, homologous to glans penis Female reproductive cycles Ovarian and uterine 1. Question: The gamete in “5” is what a. Secondary oocyte Female – ovarian cycle Ovarian cycle – monthly events associated with maturation of egg o Follicular phase (days 114, variable depending on a person and stress) Primordial follicle primary follicle Oocyte enlarges Follicle cells around primary oocyte become cuboidal Primary follicle secondary follicle Follicle cells proliferate into multiple layers (= granulosa cells) Secondary follicle late secondary follicle Formation of theca folliculi (layer of connective tissue around follicle) Thecal cells produce androgens, granulosa cells convert to estrogens Formation of zona pellucida (glycoprotein substance secreted by oocyte that forms a layer around oocyte) Late secondary follicle vesicular follicle Formation of antrum (fluidfilled cavity between granulosa cells) o Ovulation Vesicular follicle ruptures Secondary oocyte is expelled into fallopian tube o Luteal phase (1528, duration is set) Remaining follicle (thecal and granulosa cells) form into corpus luteum Corpus luteum secretes progesterone and estrogen If no pregnancy, the corpus luteum degenerates ~10 days, leaving only corpus albicans (scar) If pregnancy, the corpus luteum produces hormones until the placenta takes over (~3 months) Female – uterine cycle Uterine (menstrual) cycle – monthly changes inn uterine environment o Menstrual phase (days 15) – uterus sheds all but the deepest part of the endometrium, estrogen/progesterone levels low o Proliferative (preovulatory) phase (days 614) – rising levels of estrogen cause endometrium to rebuild itself and cervical mucus thins o Secretory (postovulatory) phase (days 1528) – rising levels of progesterone increase vascularization of endometrium, prepares it for implantation of embryo, endometrial glands enlarge cervical mucus thickens o If no pregnancy – progesterone levels fall and endometrium prepares for menstrual phase Female – hormone regulation of cycles Major hormones involved: o Gonadotropinreleasing hormone (GnRH) – stimulates anterior pituitary to release follicle stimulating hormone (FSH) and luteinizing hormone (LH) o FSH – stimulates follicle growth o LH – stimulates follicle maturation, stimulates thecal cells to produce androgens and causes ovulation o Estrogen – “sex” hormone, analogous to testosterone Promote oogenesis and follicle growth Induce secondary sexual characteristics Growth of breasts Increased fat deposition around hips and breasts Widening of pelvis Promotes endometrial growth during proliferative phase of uterine cycle o Progesterone – “sex” hormone; promote secretory phase of menstrual cycle Female – early to mid follicular phase GnRH causes FSH and LH secretion FSH binds to receptors on granulosa cells, promoting follicular growth and proliferation LH causes thecal cells to secrete androgens o Androgens converted to estrogen in granulosa cells Negative feedback of estrogen stop rise of FSH and LH o Positive feedback of estrogen onto the granulosa cells allows continued production of E when LH and FSH are low Female – late follicular phase and ovulation A dominant follicle begins to secrete high levels of E Granulosa cells start to secrete inhibin and small amount of P o Inhibin suppresses FSH E now exerts a positive feedback on hypothalamus and pituitary o Rise in E thickens endometrium o LH surges (and to lesser extent FSH) LH surge: o Oocyte complete meiosis I becoming secondary oocyte o Triggers ovulation o Ruptured follicle becomes corpus luteum Female – early to mid luteal phase Corpus luteum secretes E, P, and inhibin o Feedback negatively on hypothalamus and pituitary Progesterone: o Prepares endometrium for implantation o Thickens cervical mucus Female – late luteal phase If no fertilization o Corpus luteum degenerates o Estrogen and progesterone levels drop o This releases negative feedback and FSH and LH levels begin to rise New follicles begin to develop Female reproductive system – mammary glands Function: produce milk to nourish newborn Modified sweat glands (technically part of the integumentary system) o Areola – ring of pigmented skin o Nipple – protrusion with openings to lactiferous ducts o Lobes – 1520 per breast, made up of lobules and ducts o Lobules – contain alveoli (hollow cavities) with secretory cells (produce milk) and myoepithelial cells (milk letdown) o Lactiferous ducts – carry milk to openings in nipples o Lactiferous sinus – store milk Female pathologies Ectopic pregnancy – zygote implanted in peritoneal cavity/distal portion of tube Pelvic inflammatory disease o Infection in peritoneal cavity Scarring of uterine tubes/ovaries o STI (e.g. gonorrhea) can escape uterine tubes Cervical cancer – cancer of cervix o Risk factors: cervical inflammations, STI (ex. HPV), multiple pregnancies o Detection: pap smear Breast cancer – typically arise in epithelial cells of ducts o Risk factors: early onset menstruation and late menopause, no pregnancies (or later in life), no (or short period) breastfeeding, genetics o Detection: routine monthly breast exam, mammograms o Treatment: radiation, chemotherapy, drug therapy, lumpectomy, mastectomy Hormonal contraception Estrogen and progestin (progesterone mimic) Constant intermediate level = reduced HPG activity o Oocyte is not released from ovary o Cervical mucous thickens, reduced sperm o Alters endometrium Side effects o Weight gain o Sore breasts o Irregular menstrual flow o Nausea o Acne o Mood changes/decreased libido Development of reproductive system Genetic sex determined by sex chromosomes – XY or XX (we have 44 autosomes + 2 sex chromosomes) o Males = XY; Females = XX SRY (sexdetermining region of the Y) gene o Development of male reproductive structures 5 to 6 week old fetus Gonadal ridge – future gonads for both male and female Metanephros (kidney) – future female reproductive ducts; Fallopian tube, uterus, cervix, upper 1/3 of vagina Mesonephric (Wolffian) duct – future male reproductive ducts; epididymis, ductus (vas) deferens, and seminal vesicles Paramesonephric (Mullerian duct) Genital tubercle – small projection on external surface; gives rise to external genitalia Labioscrotal swelling – swelling inferolateral to genital tubercle Male development Male development begins in week 7 o Mullerian ducts regress o Testes from gonadal ridges o Seminiferous tubules form in gonadal ridges and join Wolffian ducts via efferent ductules o Wolffian ducts develop External genitalia begins developing in week 8 o Penis forms from genital tubercle o Labiocscrotal swellings orm the scrotum ~2 months before birth, testes to descend from abdominal cavity into scrotum Female development o If SRY gene is absent, this stimulates female development. Female is the default sex. o Development begins at week 8 o Wolffian ducts regress o Ovaries form rom gonadal ridges o Mullerian ducts develop o External genitalia begins to develop o Clitoris forms from genital tubercle o Labioscrotal swellings become the labia majora Reproductive System II o Fertilization – sperm’s chromosomes combine with chromosomes of secondary oocyte forming a zygote (the initial cell) o Oocyte – viable 1224 hours post ovulation o Sperm – viable 2448 hours after ejaculation o How many days per month is a woman fertile o 3 days Fertilization o Fate of sperm: o Leak out of vagina o Destroyed by acidic environment in vagina o Blocked at the cervix o Phagocytes destroy them o Peristalsis guides sperm to oocyte (~100 to few thousand) & secretions in female reproductive tract capacitate sperm Process of fertilization o Sperm: enzymes digest junctions between granulosa cells o Sperm binds to receptors on zona pellucida o Acrosomal reaction – acrosomoal enzymes digest holes through the zona pellucida o One sperm binds and fuses to the plasma membrane of oocyte o Cytoplasmic contents of sperm enter oocyte o Oocyte completes meiosis II o Cortical reaction prevents polyspermy o Enzymes released by oocyte destroy its sperm receptors o Zona pellucida hardens o The two nuclei fuse forming the zygote Pregnancy and developmental periods o Pregnancy – events that occur from fertilization until infant is born o Gestation period – length of time woman is pregnant; ~280 days o Embryonic period – fertilization to week 8 o Fetal period – week 9 to birth Embryonic development: cleavage o Cleavage – period of rapid mitotic divisions o 36 hours: 1 cleavage creates 2 identical cells = blastomeres o 72 hours: morula (16 or more cells) o 45 days: blastocyst: Cluster of ~100 cells Fluidfilled cavity Zona pellucida breaks down Trophoblast – single layer of large, flattened cells; aids implantation, role in placenta formation, protect embryo from mother’s immune system Inner cell mass – internal cluster of 2030 cells; forms embryo and 3 extraembryonic membranes o 67 days: implantation of blastocyst into endometrium begins Maintenance of pregnancy o At implantation: o Human chorionic gonadotropin (hCG) – from trophoblast, stimulates corpus luteum E and P Pregnancy test o Postimplantation: o Chorion develops from trophoblast, takes over stimulating corpus luteum Development: Extraembryonic membranes o We are descended from egg layers… amniotes o Yolk sac From inner cell mass Nutrients to developing embryo o Amnion From inner cell mass of blastocyst Transparent sac, fills with amniotic fluid Protection, temperature regulation o Allantois forms as outpocket from end of yolk sac blood vessels become part of umbilical cord becomes part of urinary bladder o chorion from trophoblast develops chorionic villi that form part of placenta Embryonic development: gastrulation o gastrulation – formation of 3 primary germ layers o primary germ layers: o ectoderm becomes: epidermis, hair, nails, skin glands brain and spinal cord o endoderm becomes: epithelial linings of digestive, respiratory, urogenital systems and associated glands o mesoderm becomes: everything else Developmental milestones o between 23 months – placenta fully formed and functional o 5 weeks – brain, spinal cord, other organs developing, heart begins beating o 8 weeks – arms, legs, face developing o 912 weeks – head dominant, retina of eye forms, genital sex evident, hematopoiesis begins o 1316 weeks – eyes and ears developing, body growth, bones distinct o 1720 weeks – movements o 2130 weeks – substantial weight gain / fetus viable ~24 weeks o 3140 weeks – slowed weight gain, subcutaneous fat being deposited Parturition (Birth) Labor – series of events that expel infant from uterus 3 parts o Initiation Rise in estrogen oxytocin receptors in cells of myometrium Estrogen causes Braxton Hicks contractions Fetus begins producing oxytocin: Stimulate placenta to release prostaglandins Oxytocin and prostaglandins stimulate rhythmic contractions of myometrium (=real labor) + feedback loop: mother’s hypothalamus triggers release of oxytocin from posterior pituitary, more prostaglandin release from placenta greater myometrium contraction o Dilation Cervix dilates (to ~10 cm) and effaces (thins) o Expulsion Strong uterine contractions push baby out o Placental Uterus continues contracting to expel placenta and attached fetal membranes Lactation Lactation – production of milk by mammary glands Mammary gland development during pregnancy: o Ducts elongate and branch, lobuloalveolar development and growth o Due to prolactin (anterior pituitary), estrogen, progesterone, placental lactogen (placenta) Colostrum – “first milk”; immunoglobulins (antibodies), antimicrobial proteins (lactoferrin), and antibacterials (lysozyme) Composition of “true milk” (23 days after birth): o Fat, protein, sugar o Minerals o Vitamins o Hormones o Water o Immunofactors (antibodies, antimicrobials, antibacterials) o Bacteria Milk production and letdown Prolactin – stimulates milk production Oxytocin – causes milk letdown reflex o Trust, pairbonding, contentment o Wound healing Decreases the time needed to heal Being around others releases oxytocin, which helps healing o Important in “romantic attraction,” sexual arousal (especially in females) o Treatment for autism Endocrinology – Endocrine System Ch. 16 Overview – endocrine vs. exocrine glands 1. Endocrine: ductless glands a. Secrete: hormones – chemical messenger i. Bloodstream or in an extracellular fluid then diffuse into bloodstream ii. Receptors bind hormones response b. Ex: pituitary gland, pancreas, ovaries, testes, thyroid gland, adrenal glands 2. Exocrine: nonhormonal components to membrane surface (body cavity, lumen of organ or body surface) through ducts a. Ex: salivary glands, mammary glands, chief cells in stomach, liver, and pancreas b. *pancreas is both endocrine and exocrine Hormones vs. paracrines and autocrines Hormones – chemical messengers released into bloodstream or ECF (and then diffuse into bloodstream) o circulate throughout body, receptors to respond Autocrines – chemical messengers, exert effect on cells that secrete them o Ex: prostaglandins in smooth muscle Paracrines – chemical messengers, exert effect on nearby cells o Act locally o Ex: somatostatin in pancreas inhibits insulin from Beta cells Compared to nervous system, endocrine system: o Releases hormones (vs. neurotransmitter) o Has a systemic effect (vs. localized) o Takes minutes or hours for effect (vs. milliseconds) o Effects long lasting: hours, days, years (vs. shortlived) o Regulates long term metabolic functions (vs. shortterm muscle/gland activity) Overview – functions Maintenance of overall homeostasis and reproduction negative feedbacks! o Maintains the internal environment in the body (the optimum biochemical environment) o Influences metabolic activities o Integrates and regulates growth and development o Controls, maintains stimulates sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth and development, and nourishment of the newborn Overview – types of hormones Amino acid derivatives (amines) – from amino acid tyrosine o Are water soluble o Ex: thyroid hormones o Epinephrine/norepinephrine (from adrenal medulla) Peptide hormones – consist of short or long chains of amino acids o Are water soluble o Ex: thyrotropinreleasing hormone (TRH, from hypothalamus) o ADH (from posterior pituitary) o Oxytocin (from posterior pituitary) o Growth hormone (from anterior pituitary) o LH, FSH (both from anterior pituitary) Lipid derivatives – are lipid soluble o Steroid hormones – constructed from cholesterol Ex: estrogen, testosterone, progesterone (from gonads), glucocorticoids (from adrenal cortex) o Eicosanoids – made from fatty acids Ex: prostaglandins (from cells throughout body) How hormones work – target cell activation Target cells – activity is altered by the hormone Activation depends on 3 factors: o Blood levels of the hormone which depend on: Rate of synthesis/secretion Levels of binding plasma proteins (for lipidsoluble hormones) Clearance rate (halflife) o Relative number of receptors on the target cell Upregulation – target cells form more receptors in response to increasing blood levels of hormone Downregulation – target cells lose receptors in response to high levels of hormone o Affinity of receptors for the hormone Mechanism of hormone action In general, hormones can act on target cells in 1 of 2 ways: o Secondary messenger (involves regulatory G proteins): aminoacid derived and peptide hormones (watersoluble, hydrophilic hormones) Steps Hormone binds to a Gproteinlinked receptor on the plasma membrane Hormone binding activates the Gprotein Gprotein binds to an enzyme, activating the enzyme to produce second messenger, such as cAMP Second messenger activates or inactivates enzymes in the cell o Activate genes: steroid and thyroid hormones (lipidsoluble, hydrophobic hormones) Steps Diffuse through plasma membrane of cells Bind receptor in cytoplasm or nucleus hormonereceptor complex (hrc) o Enters nucleus In nucleus, hrc binds to specific region of DNA Either turn genes “on” or “off” 1. Question: Which type of hormone utilizes a Gprotein coupled receptor on its target cell a. Hydrophilic hormones 2. Question: Which of the following form a hormonereceptor complex to alter a target cell a. Testosterone Effects of hormones Hormones produce one or more of the following cellular changes in target cells: o Alter plasma membrane permeability by opening or closing ion channels Ex: epi, norepi opens Ca channels on heart o Increase or decrease the rate of synthesis of enzyme or proteins o Activate or deactivate enzymes Ex: glucagon activates enzymes that catabolize glycogen o Induce secretory activity Ex: progesterone on cervical mucus production during secretory phase of uterine cycle o Stimulate mitosis Ex: growth hormone on skeletal muscles Control of endocrine activity Hormones are synthesized and released in response to: o Humoral stimuli – a direct response to changes in blood levels of a certain ion or nutrient Ex: low blood Ca causes secretion of parathyroid hormone o Neural stimuli – nerve fibers stimulate hormone release Sympathetic NS stimulates epinephrine and norepinephrine secretion from adrenal medulla o Hormonal stimuli – endocrine organ secrete hormones in response to hormones from another endocrine organ GnRH from hypothalamus LH and FSH from anterior pituitary estrogen from ovaries Pituitary Gland (hypophysis) 1. Connected to hypothalamus by infundibulum 2. Consists of 2 major lobes: a. Anterior pituitary – composed of glandular tissue, produce/secrete many hormones b. Posterior pituitary – composed of neural tissue, stores and releases hormones produced by hypothalamus Hypothalamicpituitary axis Hypothalamicpituitary relationship o Anterior pituitary No direct neural connection to hypothalamus Vascular connection – hypophyseal portal system (2 capillary beds connected by veins) 6 hormones produced (all protein): luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroidstimulating hormone (TSH), and growth hormone (GH) Steps Secretion of regulatory hormones from hypothalamic neurons Regulatory hormone travel through hypophyseal portal system into the anterior pituitary Hormones from anterior pituitary released into capillaries o Posterior pituitary Maintains neural connection with hypothalamus – hypothalamic hypophyseal tract 2 hormones released: antidiuretic hormone (ADH), oxytocin Steps: Hypothalamus synthesizes Stored in posterior pituitary within axon terminals of hypothalamic neurons Released in response to action potentials from the hypothalamic neurons Pathologies: growth hormone 1. Gigantism – hypersecretion of GH in children 2. Acromegaly – hypersecretion of GH after epiphyseal plates closed a. Overgrowth of hands, feet, face 3. Pituitary dwarfism – hyposecretion of GH a. Slows long bone growth b. May coincide with deficiencies in other pituitary hormones Hypothalamicpituitarythyroid axis 1. Thyroid glands a. Located on the trachea, just inferior to the larynx b. Inside thyroid glands i. Follicles – secrete thyroid hormones 1. Follicular cells – epithelial cells making up the walls of follicles, synthesize thyroglobulin (glycoprotein) and secrete it into the cavity 2. Follicular cavity – stores colloid (fluid with thyroglobulin and attached iodine atoms for TH synthesis) ii. Parafollicular cells 1. Secrete calcitonin – decreases blood Ca levels in animals, role not clear in humans Thyroid hormones 1. Major metabolic hormones – affects almost every cell in the body except adult brain, spleen, testes, uterus, and thyroid gland itself 2. 2 active forms of the hormone a. Thyroxine (T4) – less potent form, has 4 iodine ions, predominant TH secreted by thyroid gland, most T4 is converted to T3 at the target tissue b. Triiodothyronine (T3) – more potent form, has 3 iodine ions, small amount is produced by thyroid hormone 3. Effects a. Promote glucose catabolism, mobilizes fats b. Increases basal metabolic rate and body heat production c. Increase adrenergic receptor in blood vessels (increase sensitivity to sympathetic NS activity) d. Regulate tissue growth and development, including muscular, skeletal growth, development of NS Thyroid hormone synthesis 1. Follicular cell synthesizes enzymes and thyroglobulin, which are secreted into follicular cavity 2. Iodide ions are transported into follicle cells 3. Iodide ions then move into follicular cavity and are oxidized to iodine 4. Enzymes add iodine to thyroglobulin to make T1 (monoiodotyrosine) and T2 (diiodotyrosine) 5. Enzymes link T1 and T2 a. T1 + T2 yields T3 (triiodothyronine) b. T2 + T2 yields T4 (thyroxine) 6. Thyroglobulin endocytosed back into follicular cell 7. Enzymes cleave T3 and T4 from thyroglobulin, hormones secreted into bloodstream Control of thyroid hormone secretion 1. Stimuli for release: a. Decreased thyroid hormone levels in blood b. Low body temperature 2. Thyrotropinreleasing hormone (TRH) from hypothalamus thyroid stimulating hormone (TSH) from anterior pituitary T3 and T4 from thyroid gland 3. T3 and T4 exert negative feedback onto the hypothalamus and anterior pituitary HPT axis – pathology 1. Hyperthyroidism a. Cause i. Grave’s disease – autoimmune disease, abnormal antibodies mimic TSH b. Symptoms i. Increased BMR, heat production, sweating ii. Muscle weakness, weight loss iii. Hyperexcitable reflexes and psychological disturbances, e.g., insomnia, irritability, restlessness iv. Rapid, irregular heartbeat v. Bulging eyeballs c. Treatment i. Surgically remove thyroid ii. Consume radioactive iodine HPT axis – pathology 2. hypothyroidism (myxedema) a) cause 1. removal of thyroid gland 2. lack of iodine in the diet b) symptoms 1. feeling cold, low metabolic rate 2. slowed reflexes, slow speech and thought process 3. slow heart rate 4. goiter (enlarged thyroid gland) – insufficient iodine Follicular cells produce colloid, insufficient iodine to make T3 and T4 Pituitary increase TSH secretion more unusable colloid Reason for iodized salt c) treatment 1. iodine supplements 2. thyroid hormone replacement therapy