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

Transcription

1 Action of reproductive hormones through the life span

2 Do reproductive hormones affect the life span? One hypothesis about the rate of aging asserts that there is selective pressure for either high rate of reparative growth and longevity but low reproductive rate, or low rate of reparative growth, short life span, and high reproductive rate

3 Do reproductive hormones affect the life span? Since reproductive success is what drives natural selection, if reproduction has been carried out, there should be no additional benefit of longer lifespan A test of this hypothesis would entail examining the relationship between delayed or suppressed puberty agonadal status celibacy on longevity

4 Is the action of reproductive hormones preprogrammed? Germ line is passed on from generation to generation (it is immortal) while the soma is finite Gender is genetically preprogrammed (sex determination) Development of gonads is genetically preprogrammed (sex differentiation) Brain is developmentally programmed by exposure to sex hormones Onset of puberty is preprogrammed but somewhat modifyable

5 Cells that develop into reproductive cells or gametes In reduction division or meiosis, parental chromosomes are segregated and divided so that germ cells receive a single parental complement This preprograms genetic options for the future soma Germ cells

6 Development of germ cell line After fertilization and during 5th week of embryogenesis,, germ cells originate in the gut migrate to gonadal ridges Fetal testis differentiates during week 7 begins to secrete testosterone during week 8 testosterone influences phenotype

7 Development of germ cell line Fetal ovary forms follicles 15 of gestation estrogen secreted from w10 no effect on phenotype

8 Sex determination Chromosomal sex is predetermined Human genome is autosomes 2 sex chromosomes Female genome is 46,XX Male genome is 46,XY Gamete genome is 23X, 23X in females, and 23Y, 23X in males

9 Chromosomal sex Germ cell line is propagated to next generation After fertilization gonads develop Reduction division occurs in the gonads Germ cell line is passed on through fertilization

10 Chromosomal sex determination Y chromosome smallest with only a few genes sex-determining region of Y (SRY) on the short arm of Y chromosome primary determinant of testis development Overall sexual differentiation requires Y chromosome X chromosome autosomes

11 Is chromosomal sex determination related to longevity? Genomic study of Amish families men with deletion of a portion of the short arm of Y chromosome have longer life span than Amish women

12 After fertilization and during 5th week of embryogenesis, germ cells originate in the gut migrate to gonadal ridges Fetal testis differentiates during week 7 begins to secrete testosterone during week 8 testosterone influences phenotype Fetal ovary forms follicles 15 of gestation estrogen secreted from w10 no effect on phenotype Development of gonadal sex

13 Phenotypic sex: gender differences phenotypic sex (internal genitalia) both genders have similar dual genital-duct systems prior to week 8 of gestation after week 8 male and female internal genitalia develop from different precursors Mullerian duct: F Wolffian duct: M Female phenotype develops when testo is absent

14 Phenotypic sex: gender differences phenotypic sex (external genitalia) both genders have similar external genital structures prior to week 6 of gestation testosterone causes closure of genital folds development of penis Female phenotype develops when testosterone is absent

15 Chromosomal preprogramming drives gonadal and phenotypic differentiation Female phenotype develops in the absence of sex hormones Testosterone is necessary for male phenotype Testosterone guides differentiuation of male gonad Testosterone differentiates brain function Phenotypic mixups occur when development occurs in inappropriate hormonal environment

16 Mixups in chromosomal sex Klinefelter syndrome : 47,XXY (M) predominantly male phenotype small testes no spermatogenesis gynecomastia low testosterone, elevated estradiol

17 Mixups in chromosomal sex Turner s syndrome : 45,X (gonadal dysgenesis) female phenotype gonadal atrophy external genitalia immature internal genitalia underdeveloped poor growth

18 Mixups in gonadal sex pure gonadal dysgenesis :46,XX(F)or XY(M) chromosomal sex is normal may have mutations on SRY gene gonads fail to differentiate phenotypic females estrogen deficiency normal height

19 Mixups in phenotypic sex Female pseudohermaphroditism excessive virilization of female embryo adrenal hyperplasia due to overstimulation of testosterone pathway due to undersecretion of cortisol internal genitalia F, external genitalia M

20 Mixups in phenotypic sex Male pseudohermaphroditism male genome inadequate virilization of male embryo due to defects in testosterone pathway in the testis testosterone action (receptors) internal genitalia F, external genitalia F

21 Preprogrammed actions of reproductive hormones Fetal pituitary makes and secretes LH and FSH from week 5 on Gonadotropin secretion is high during the first year of life It declines during childhood due to a brain inhibitory mechanism It rises after age 12 years as a prelude to puberty The same pattern occurs in agonadal females

22 Preprogrammed actions of reproductive hormones Puberty is initiated by nocturnal increases in LH secretion

23 Preprogrammed actions of reproductive hormones In the female, icreased gonadotropin stimulates the ovary to produce increasing amounts of estradiol.. In the male, increasing amt of testo. Increased estradiol titers stimulate development of reproductive organs, breasts cyclical pattern of gonadotropin secretion adolescent (prepubertal( prepubertal) ) growth spurt In the male, corresponding development of reproductive organs and growth spurt.

24 How do gender differences develop? At puberty, gonadal hormones increase GH secretion increased GH secretion accelerates somatic and skeletal growth growth stimulation is greater in males than in females and differentially affects several body components skeleton muscle body fat

25 Growth spurt, growth cessation and puberty are connected Mean weight needed to initiate growth spurt is 30 kg at peak growth velocity is 39 kg at the onset of puberty is 47 kg for all these events is the same in early and late maturing girls

26 Growth spurt, growth cessation and puberty are connected Critical weight (or fat to lean ratio) is necessary for initiation of puberty Neural control of gonadotropin release changes (reduced negative feedback of estradiol increases gonadotropin release) Energy regulation changes (metabolic rate per unit mass declines)

27 Preprogrammed actions of reproductive hormones At puberty, secretion of hypothalamic gonadotrophin releasing hormone increases pituitary gonadotrophins increases secretion of gonadal steroids increases GH secretion increases in part in response to increased gonadal steroids

28 Can the reproductive programming be changed? Undernutrition and reduced critical weight can delay the onset of puberty (primary amenorrhea) Energy drain of heavy training in adolescence can delay the onset of puberty Delayed onset of puberty prolongs the period of growth Delayed growth is more marked in the appendicular skeleton

29 Reproductive cycle in the female Hormonal and endometrial changes during a menstrual cycle follicular phase ovulation corpus luteum (CL) secretes estrogen and progesterone luteal phase menstruation to hormone withdrawal

30 reduce the LH pulse frequency changed LH pulse frequency causes an inadequate follicle Inadequate follicle develops into an inadequate CL Inadequate CL secretes progesterone for a shorter time and produces shorter luteal phase Heavy training or undernutrition:

31 Amenorhea: shortened luteal phase

32 Amenorhea: prevalence by sport

33 Amenorhea: fat loss

34 Can reproduction and gender differences affect mortality? Does reproduction curtail life span and celibacy lengthen it? Reproduction can increase morbidity childbirth complications estrogen exposure increases risk of cancer of breats,, uterus testosterone exposure increases risk of prostate cancer

35 Gender differences and health risk factors : biology or lifestyle HDL (M>F) coronary heart disease (M>F) arthritis (F>M) obesity (F>M) inactivity (F>M)

36 More gender differences Cardiac output of women is about 10% smaller smaller heart volume Resting heart rate is about 5% higher in women Maximal heart rate is about 2% lower in women

37 More gender differences The volume of blood is about 20% lower in women for the same body weight For the same volume of blood, women have about 10% less hemoglobin 16 g/dl in men 14 g/dl in women difference in oxygen carrying capacity of blood (1.34 ml oxygen binds to each g of Hb)

38 More gender differences The vital capacity of a woman is about 10% lower than that of a man

39 More gender differences The wider pelvis of a woman decreases mechanical efficiency by increasing the angle of the thigh bone to bring the knees closer together greater incidence of knee injuries in sports The Achilles tendon, which is important in the elastic recoil of running, is shorter in women

40 More gender differences For the same body weight, the average female possesses about 10% more fat than the average male, which increases the load to be carried

41 More gender differences For the same body weight, the average female possesses about 10% less muscle than the average male, which reduces how heavy a load can be carried Females utilize more lipids than men during exercise

42 What can we conclude? Reproductive hormones may affect the lifespan Action of reproductive hormones, like the growth hormone, is preprogrammed GH and reproductive hormone programming is interrelated Reproductive hormone programming can be altered by exercise and nutrition Withdrawal of reproductive hormones accelerates secondary aging