1. Lecture 43: What are the functions of the sex hormones?
Puberty Onset:
Gonadostat & GnRH
Secondary Sex Traits
Cholesterol  Steroids
Aromatase
Male Sex Hormones
Female Sex Hormones
Menopause & Andropause
Visceral Obesity & Leptin
Male Fertility
Dr. Karen Petersen, Biol. 118, Autumn 2016
12/8/15

2. How do GnRH neurons alter in their sensitivity to negative feedback at the onset of puberty?
“Gonadostat”: sensitivity to negative feedback
LH, FSH: relative to adult levels
Adrenarche = rise in androgens
Evidence for early puberty in boys
High BMI gain during childhood is related to an earlier onset of puberty and reduced height gain during adolescence, whereas boys with a later onset of puberty tend to be taller and less obese as adults19,61
■■A trend towards earlier voice break occurs with increasing BMI SD score62
■■Mean age at onset of puberty had declined significantly during a recent 15 year interval in a study of Danish boys and this decline was associated with an increase in BMI58
■■Delayed puberty in overweight boys might modulate adult height and the etiology of delayed puberty differs from typical constitutional delay17,19,65
■■The majority of studies in which the relationship between obesity and puberty was analyzed show obesity to be associated with earlier puberty but inconsistencies remain and future research is needed
Box 2 | Obesity and timing of puberty in girls
■■More evidence exists in girls than in boys that obesity leads to an earlier timing of puberty
■■A direct relationship exists between BMI and measures of pubertal onset (breast development and menarche)55,66,67,68
■■Research suggests that earlier puberty in girls might be caused by obesity, rather than that earlier puberty causes an increase in body adipose tissue69,70
■■Small size at birth and childhood obesity have been found to be associated with a young age of menarche in girls; this effect appears to be consistent across different ethnicities73,76
■■Questions remain concerning how obesity, timing of puberty and progression of puberty are mechanistically linked in girls
Wagner, Sabin, Pfäffle, et al, 2012
12/8/15

3. What physical & hormonal changes occur during puberty?
&
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4. Which hormones are derived from cholesterol?
Explain why extremely low body fat leads to amenorrhea in women.
Yes, fat cells produce some estrogen
Alcohol 
Aromatase inhibitors: a class of breast cancer chemotherapy. How would this drug work?

5. Explain the male sex hormones & negative feedback pathways
Compare with Fig. 19-7
Stanfield, 2013
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6. Explain the female sex hormones & feedback pathways
Early Follicular Phase
Nurse cells
Nurse cells
Compare with Fig
Stanfield, 2013

7. Ovulation & Late Follicular Phase
Luteal (Post-Ovulation) Phase
Nurse cells
Compare with Fig
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Stanfield, 2013

8. How & why do sex hormone levels change with age?
Female
Childhood
Adulthood
Menopause
Male: Testosterone
Predict the FSH, LH, GnRH values in older males.
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9. How does visceral obesity alter sex hormones in men?
Erectile dysfunction
Higher scrotal T. 
Lower sperm counts
Higher aromatase 
Higher estradiol
Lower testosterone
Higher insulin  higher estradiol
Higher leptin 
inhibitory
inhibitory
12/8/15
Du Plessis, et al. 2010
Davidson, Millar, Jones, et al. 2015

10. Topics to understand & review:
Explain how “sex” hormones increase from low levels in childhood to higher values with puberty. Compare primary & secondary sex traits of males & females.
Trace the conversion of these substances from cholesterol, including other intermediate substances: testosterone, progesterone & estrogens. What is the function of the enzyme aromatase? Why are aromatase inhibitors used to treat some forms of breast cancer?
Describe the hormonal pathways regulating sperm production production in a male. Why is negative feedback used? How will this cause stable sperm production?
Describe the hormones in a female’s ovarian & uterine cycles. Know where is each hormone is produced, its target(s) & its functions. What factors may cause amenorrhea? What other problems may be associated with a long-term failure to menstruate?
Describe the time delay in LH release. . Graph the average values of these hormones over a month in a female. Which hormone “spike” is critical to ovulation? What hormonal changes “cause” menstruation? Which hormone triggers growth of the uterine stratum functionalis? Which hormone peaks around ovulation, causing the cervical mucous to become thinner? Which hormone is at its peak after ovulation & makes the endometrium secrete nutrients? When is negative feedback & positive feedback affecting female cycles?
Why do women have a rapid decline in estrogen & progesterone, but increased GnRH, FSH, LH at menopause? Graph the level of testosterone secretion in a male from age years. What effect does this have on a male’s body & on sperm production? Predict the level of GnRH, FSH & LH in older males, as testosterone declines.
How does visceral obesity affect the male reproductive system? What is the role of leptin produced in fat cells? How does PCOS affect female fertility & their risk of diabetes?

11. Additional Resources
Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group Consensus on women's health aspects of polycystic ovary syndrome (PCOS). Hum Reprod. 27(1):14-24.
Barrett ES, Thune I, Lipson SF, et al A factor analysis approach to examining relationships among ovarian steroid concentrations, gonadotrophin concentrations and menstrual cycle length characteristics in healthy, cycling women. Hum Reprod. 28(3):
Brosens JJ, et al A role for menstruation in preconditioning the uterus for successful pregnancy. Am J Obstet Gynecol. 200:615.e1-615.e6.
Bukovsky A Ovarian stem cell niche and follicular renewal in mammals. Anat Rec (Hoboken). 294(8):
Cooper TG, Noonan E, Eckardstein S, et al World Health Organization reference values for human semen characteristics. Hum. Reprod. Update 16 (3):
Davidson LM, Millar K, Jones C, et al Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility. Human Fertility 18(3): 184–193.
Du Plessis, SS et al The effect of obesity on sperm disorders and male infertility. Nat Rev Urol 7:
Emera D, Romero R, & Wagner G The evolution of menstruation: A new model for genetic assimilation: Explaining molecular origins of maternal responses to fetal invasiveness. Bioessays 34(1):26-35.
Esteves SC, Zini A, Aziz N, et al Critical appraisal of World Health Organization's new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. Urology 79(1):16–22.
Jayasena CN & Franks S The management of patients with polycystic ovary syndrome. Nature Reviews Endocrinology 10, 624–636.
Redmon JB, Thomas W, Ma W, et al Semen parameters in fertile US men: the Study for Future Families. Andrology 1(6):806–814.
Renfree MB Why menstruate? Bioessays 34(1):1
Silverthorn DU Human Physiology: An Integrated Approach. 4 ed. Pearson Publ.
Stanfield CL Principles of Human Physiology, 5 Ed. Wiley-Blackwell, Publ.
Stephens SM, Polotsky AJ Big enough for an aromatase inhibitor? How adiposity affects male fertility. Semin Reprod Med. 31(04):
Teerds KJ, de Rooij DG, & Keijer J Functional relationship between obesity and male reproduction: from humans to animal models. Human Reproduction Update 17(5):667–683.
Wagner IV, Sabin MA, Pfäffle RW, et al Effects of obesity on human sexual development. Nat. Rev. Endocrinol. 8:246–254.
Environmental Endocrine Disrupters/Mimics: