Action of reproductive hormones through the life spankcourses/f99/mvs443/Reproduction/...9/22/99 Do...

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9/22/99 Action of reproductive hormones through the life span

Transcript of Action of reproductive hormones through the life spankcourses/f99/mvs443/Reproduction/...9/22/99 Do...

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Action of reproductive hormonesthrough the life span

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Do reproductive hormones affectthe life span?

nn One hypothesis about the rate of aging asserts thatOne hypothesis about the rate of aging asserts thatthere is selective pressure for eitherthere is selective pressure for eitheruu high rate of reparative growth and longevity but lowhigh rate of reparative growth and longevity but low

reproductive rate, orreproductive rate, oruu low rate of reparative growth, short life span, and highlow rate of reparative growth, short life span, and high

reproductive ratereproductive rate

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Do reproductive hormones affectthe life span?

nn Since reproductive success is what drives naturalSince reproductive success is what drives naturalselection, if reproduction has been carried out,selection, if reproduction has been carried out,there should be no additional benefit of longerthere should be no additional benefit of longerlifespanlifespan

nn A test of this hypothesis would entail examiningA test of this hypothesis would entail examiningthe relationship betweenthe relationship betweenuu delayed or suppressed pubertydelayed or suppressed pubertyuu agonadalagonadal status statusuu celibacycelibacy

on longevityon longevity

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Is the action of reproductivehormones preprogrammed?

nn Germ line is passed on from generation toGerm line is passed on from generation togeneration (it is immortal) while the soma is finitegeneration (it is immortal) while the soma is finite

nn Gender is genetically preprogrammed (sexGender is genetically preprogrammed (sexdetermination)determination)

nn Development of gonads is geneticallyDevelopment of gonads is geneticallypreprogrammed (sex differentiation)preprogrammed (sex differentiation)

nn Brain is developmentally programmed byBrain is developmentally programmed byexposure to sex hormonesexposure to sex hormones

nn Onset of puberty is preprogrammed but somewhatOnset of puberty is preprogrammed but somewhatmodifyablemodifyable

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Germcellsnn Cells that develop intoCells that develop into

reproductive cells orreproductive cells orgametesgametes

nn In reduction division orIn reduction division ormeiosis, parentalmeiosis, parentalchromosomes arechromosomes aresegregated and dividedsegregated and dividedso that germ cells receiveso that germ cells receivea single parentala single parentalcomplementcomplement

nn This preprograms geneticThis preprograms geneticoptions for the futureoptions for the futuresomasoma

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Development of germ cell line

nn After fertilization and during 5th week ofAfter fertilization and during 5th week ofembryogenesisembryogenesis, germ cells, germ cellsuu originate in the gutoriginate in the gutuu migrate tomigrate to gonadal gonadal ridges ridges

nn Fetal testisFetal testisuu differentiates during week 7differentiates during week 7uu begins to secrete testosterone during week 8 begins to secrete testosterone during week 8uu testosterone influences phenotypetestosterone influences phenotype

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Development of germ cell line

nn Fetal ovary forms folliclesFetal ovary forms folliclesuu 15 of gestation15 of gestationuu estrogen secreted from w10estrogen secreted from w10uu no effect on phenotypeno effect on phenotype

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Sex determinationChromosomal sex is predetermined

nn Human genome is 46Human genome is 46uu 4444 autosomes autosomesuu 2 sex chromosomes2 sex chromosomes

nn Female genome is 46,XXFemale genome is 46,XXnn Male genome is 46,XYMale genome is 46,XYnn Gamete genome isGamete genome isuu 23X, 23X in females , and23X, 23X in females , anduu 23Y, 23X in males23Y, 23X in males

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Chromosomal sex

nn Germ cell line is propagated to nextGerm cell line is propagated to nextgenerationgeneration

nn After fertilization gonads developAfter fertilization gonads developnn Reduction division occurs in the gonadsReduction division occurs in the gonadsnn Germ cell line is passed on throughGerm cell line is passed on through

fertilizationfertilization

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Chromosomal sex determinationnn Y chromosomeY chromosomeuu smallest with only a few genessmallest with only a few genesuu sex-determining region of Y (SRY)sex-determining region of Y (SRY)uu on the short arm of Y chromosomeon the short arm of Y chromosomeuu primary determinant of testis developmentprimary determinant of testis development

nn Overall sexual differentiation requiresOverall sexual differentiation requiresuu Y chromosomeY chromosomeuu X chromosomeX chromosomeuu autosomesautosomes

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Is chromosomal sex determinationrelated to longevity?

nn GenomicGenomic study of Amish families study of Amish familiesuu men with deletion of a portion of themen with deletion of a portion of the

short arm of Y chromosome haveshort arm of Y chromosome havelonger life span than Amish womenlonger life span than Amish women

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Development ofgonadal sex

nn After fertilization and duringAfter fertilization and during5th week of5th week of embryogenesis embryogenesis,,germ cellsgerm cellsuu originate in the gutoriginate in the gutuu migrate tomigrate to gonadal gonadal ridges ridges

nn Fetal testisFetal testisuu differentiates during week 7differentiates during week 7uu begins to secrete testosterone begins to secrete testosterone

during week 8during week 8uu testosterone influencestestosterone influences

phenotypephenotype

nn Fetal ovary forms folliclesFetal ovary forms folliclesuu 15 of gestation15 of gestationuu estrogen secreted from w10estrogen secreted from w10uu no effect on phenotypeno effect on phenotype

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Phenotypic sex: genderdifferences nn phenotypic sex (internalphenotypic sex (internal

genitalia)genitalia)uu both genders have similarboth genders have similar

dual genital-duct systemsdual genital-duct systemsprior to week 8 of gestationprior to week 8 of gestation

uu after week 8 male andafter week 8 male andfemale internal genitaliafemale internal genitaliadevelop from differentdevelop from differentprecursorsprecursorsFF MullerianMullerian duct: F duct: FFF WolffianWolffian duct: M duct: M

nn Female phenotypeFemale phenotypedevelops whendevelops when testo testo is isabsentabsent

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Phenotypic sex: genderdifferences nn phenotypic sexphenotypic sex

(external genitalia)(external genitalia)uu both genders haveboth genders have

similar external genitalsimilar external genitalstructures prior tostructures prior toweek 6 of gestationweek 6 of gestation

uu testosterone causestestosterone causesFF closure of genital folds closure of genital foldsFF development of penisdevelopment of penis

uu Female phenotypeFemale phenotypedevelops whendevelops whentestosterone is absenttestosterone is absent

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Chromosomal preprogramming drivesgonadal and phenotypic differentiation

nn Female phenotype develops in the absence of sexFemale phenotype develops in the absence of sexhormoneshormones

nn Testosterone is necessary for male phenotypeTestosterone is necessary for male phenotypenn Testosterone guidesTestosterone guides differentiuation differentiuation of male gonad of male gonadnn Testosterone differentiates brain functionTestosterone differentiates brain functionnn PhenotypicPhenotypic mixups mixups occur when development occur when development

occurs in inappropriate hormonal environmentoccurs in inappropriate hormonal environment

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Mixups in chromosomal sex

uuKlinefelterKlinefelter syndrome : 47,XXY (M) syndrome : 47,XXY (M)••predominantly male phenotypepredominantly male phenotype••small testessmall testes••no spermatogenesisno spermatogenesis••gynecomastiagynecomastia••low testosterone, elevatedlow testosterone, elevated estradiol estradiol

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Mixups in chromosomal sex

uuTurner’s syndrome : 45,XTurner’s syndrome : 45,X((gonadal dysgenesisgonadal dysgenesis))FF female phenotypefemale phenotypeFF gonadalgonadal atrophy atrophyFF external genitalia immatureexternal genitalia immatureFF internal genitalia underdevelopedinternal genitalia underdevelopedFF poor growthpoor growth

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Mixups in gonadal sexnn purepure gonadal dysgenesis gonadal dysgenesis :46,XX(F)or :46,XX(F)or

XY(M)XY(M)uu chromosomal sex is normalchromosomal sex is normaluu may have mutations on SRY genemay have mutations on SRY geneuu gonads fail to differentiategonads fail to differentiateuu phenotypic femalesphenotypic femalesuu estrogen deficiencyestrogen deficiencyuu normal heightnormal height

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Mixups in phenotypic sex

nn FemaleFemale pseudohermaphroditism pseudohermaphroditismuu excessiveexcessive virilization virilization of female embryo of female embryouu adrenaladrenal hyperplasia hyperplasia due to due to overstimulation overstimulation of of

testosterone pathway due totestosterone pathway due to undersecretion undersecretion of ofcortisolcortisol

uu internal genitalia F, external genitalia Minternal genitalia F, external genitalia M

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Mixups in phenotypic sexnn MaleMale pseudohermaphroditism pseudohermaphroditismuu male genomemale genomeuu inadequateinadequate virilization virilization of male embryo of male embryouu due to defectsdue to defects

FF in testosterone pathway in the testis in testosterone pathway in the testisFF testosterone action (receptors)testosterone action (receptors)

uu internal genitalia F, external genitalia Finternal genitalia F, external genitalia F

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Preprogrammed actions ofreproductive hormones

nn Fetal pituitary makes and secretes LH and FSHFetal pituitary makes and secretes LH and FSHfrom week 5 onfrom week 5 on

nn GonadotropinGonadotropin secretion is high during the first secretion is high during the firstyear of lifeyear of life

nn It declines during childhood due to a brainIt declines during childhood due to a braininhibitory mechanisminhibitory mechanism

nn It rises after age 12 years as a prelude to pubertyIt rises after age 12 years as a prelude to pubertynn The same pattern occurs inThe same pattern occurs in agonadal agonadal females females

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Preprogrammed actions ofreproductive hormones

nn Puberty isPuberty isinitiated byinitiated bynocturnalnocturnalincreases in LHincreases in LHsecretionsecretion

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Preprogrammed actions ofreproductive hormonesnn In the female,In the female, icreased gonadotropin icreased gonadotropin stimulates stimulates

the ovary to produce increasing amounts ofthe ovary to produce increasing amounts ofestradiolestradiol. In the male, increasing. In the male, increasing amt amt of of testo testo..

nn IncreasedIncreased estradiol estradiol titers stimulate development of titers stimulate development ofuu reproductive organs, breastsreproductive organs, breastsuu cyclical pattern ofcyclical pattern of gonadotropin gonadotropin secretion secretionuu adolescent (adolescent (prepubertalprepubertal) growth spurt) growth spurt

nn In the male, corresponding development ofIn the male, corresponding development ofuu reproductive organs and growth spurt.reproductive organs and growth spurt.

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How do gender differencesdevelop ? nn At puberty,At puberty,

uu gonadalgonadal hormones hormonesincrease GH secretionincrease GH secretion

uu increased GH secretionincreased GH secretionaccelerates somatic andaccelerates somatic andskeletal growthskeletal growth

uu growth stimulation isgrowth stimulation isgreater in males than ingreater in males than infemales and differentiallyfemales and differentiallyaffects several bodyaffects several bodycomponentscomponentsFF skeletonskeletonFF musclemuscleFF body fatbody fat

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Growth spurt, growth cessation andpuberty are connected

nn Mean weightMean weightuu needed to initiateneeded to initiate

growth spurt is 30 kggrowth spurt is 30 kguu at peak growth velocityat peak growth velocity

is 39 kgis 39 kguu at the onset of pubertyat the onset of puberty

is 47 kgis 47 kguu for all these events isfor all these events is

the same in early andthe same in early andlate maturing girlslate maturing girls

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Growth spurt, growth cessationand puberty are connectednn Critical weight (or fat to lean ratio) isCritical weight (or fat to lean ratio) is

necessary for initiation of pubertynecessary for initiation of pubertynn Neural control ofNeural control of gonadotropin gonadotropin release release

changes (reduced negative feedback ofchanges (reduced negative feedback ofestradiolestradiol increases increases gonadotropin gonadotropin release) release)

nn Energy regulation changes (metabolic rateEnergy regulation changes (metabolic rateper unit mass declines)per unit mass declines)

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Preprogrammed actions ofreproductive hormones

nn At puberty, secretion ofAt puberty, secretion ofuu hypothalamichypothalamic

gonadotrophingonadotrophin releasing releasinghormone increaseshormone increases

uu pituitarypituitary gonadotrophins gonadotrophinsincreasesincreases

uu secretion ofsecretion of gonadal gonadalsteroids increasessteroids increases

uu GH secretion increases inGH secretion increases inpart in response topart in response toincreasedincreased gonadal gonadal steroids steroids

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Can the reproductiveprogramming be changed?nn UndernutritionUndernutrition and reduced critical weight and reduced critical weight

can delay the onset of puberty (primarycan delay the onset of puberty (primaryamenorrheaamenorrhea))

nn Energy drain of heavy training inEnergy drain of heavy training inadolescence can delay the onset of pubertyadolescence can delay the onset of puberty

nn Delayed onset of puberty prolongs theDelayed onset of puberty prolongs theperiod of growthperiod of growth

nn Delayed growth is more marked in theDelayed growth is more marked in theappendicularappendicular skeleton skeleton

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Reproductive cycle inthe female nn Hormonal andHormonal and

endometrialendometrial changes changesduring a menstrualduring a menstrualcyclecycleuu follicular phasefollicular phaseuu ovulationovulationuu corpuscorpus luteum luteum (CL) (CL)

secretes estrogen andsecretes estrogen andprogesteroneprogesterone

uu lutealluteal phase phaseuu menstruation tomenstruation to

hormone withdrawalhormone withdrawal

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Heavy training orundernutrition:

nn reduce the LH pulsereduce the LH pulsefrequencyfrequency

nn changed LH pulsechanged LH pulsefrequency causes anfrequency causes aninadequate follicleinadequate follicle

nn Inadequate follicleInadequate follicledevelops into andevelops into aninadequate CLinadequate CL

nn Inadequate CLInadequate CLsecretes progesteronesecretes progesteronefor a shorter time andfor a shorter time andproduces shorterproduces shorterlutealluteal phase phase

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Amenorhea: shortened lutealphase

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Amenorhea: prevalence by sport

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Amenorhea: fat loss

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Can reproduction and genderdifferences affect mortality?nn Does reproduction curtail life span andDoes reproduction curtail life span and

celibacy lengthen it?celibacy lengthen it?nn Reproduction can increase morbidityReproduction can increase morbidityuu childbirth complicationschildbirth complicationsuu estrogen exposure increases risk of cancer ofestrogen exposure increases risk of cancer of

breatsbreats, uterus, uterusuu testosterone exposure increases risk of prostatetestosterone exposure increases risk of prostate

cancercancer

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Gender differences and healthrisk factors : biology or lifestylenn HDL (M>F)HDL (M>F)nn coronary heart disease (M>F)coronary heart disease (M>F)nn arthritis (F>M)arthritis (F>M)nn obesity (F>M)obesity (F>M)nn inactivity (F>M)inactivity (F>M)

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More gender differences

nn Cardiac output of women is about 10%Cardiac output of women is about 10%smallersmalleruu smaller heart volumesmaller heart volume

nn Resting heart rate is about 5% higher inResting heart rate is about 5% higher inwomenwomen

nn Maximal heart rate is about 2% lower inMaximal heart rate is about 2% lower inwomenwomen

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More gender differences

nn The volume of blood is about 20% lower inThe volume of blood is about 20% lower inwomen for the same body weightwomen for the same body weight

nn For the same volume of blood , womenFor the same volume of blood , womenhave about 10% less hemoglobinhave about 10% less hemoglobinuu 16 g/dl in men16 g/dl in menuu 14 g/dl in women14 g/dl in womenuu difference in oxygen carrying capacity of blooddifference in oxygen carrying capacity of blood

(1.34 ml oxygen binds to each g of(1.34 ml oxygen binds to each g of Hb Hb))

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More gender differences

nn The vital capacityThe vital capacityof a woman isof a woman isabout 10% lowerabout 10% lowerthan that of a manthan that of a man

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More gender differences

nn The wider pelvis of a woman decreasesThe wider pelvis of a woman decreasesmechanical efficiency by increasing themechanical efficiency by increasing theangle of the thigh bone to bring the kneesangle of the thigh bone to bring the kneescloser togethercloser togetheruu greater incidence of knee injuries in sportsgreater incidence of knee injuries in sports

nn The Achilles tendon, which is important inThe Achilles tendon, which is important inthe elastic recoil of running, is shorter inthe elastic recoil of running, is shorter inwomenwomen

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More gender differences

nn For the same bodyFor the same bodyweight, the averageweight, the averagefemale possessesfemale possessesabout 10% more fatabout 10% more fatthan the averagethan the averagemale, whichmale, whichincreases the loadincreases the loadto be carriedto be carried

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More gender differencesnn For the same bodyFor the same body

weight, the averageweight, the averagefemale possesses aboutfemale possesses about10% less muscle than10% less muscle thanthe average male,the average male,which reduces howwhich reduces howheavy a load can beheavy a load can becarriedcarried

nn Females utilize moreFemales utilize morelipids than men duringlipids than men duringexerciseexercise

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What can we conclude?nn Reproductive hormones may affect theReproductive hormones may affect the lifespan lifespannn Action of reproductive hormones, like the growthAction of reproductive hormones, like the growth

hormone, is preprogrammedhormone, is preprogrammednn GH and reproductive hormone programming isGH and reproductive hormone programming is

interrelatedinterrelatednn Reproductive hormone programming can beReproductive hormone programming can be

altered by exercise and nutritionaltered by exercise and nutritionnn Withdrawal of reproductive hormones acceleratesWithdrawal of reproductive hormones accelerates

secondary agingsecondary aging