Lecture Notes, Biology 203

Lecture Notes, Biology 203, Human Sexuality and Reproduction

Hormones, Part 1

Introduction
1. Hormones: chemical substances produced by the endocrine glands and released into the blood
2. Travel through blood to reach target organ
3. Target organs have cells that have receptors that bind a specific hormone
4. Many of the hormones discussed in this class are produced by the hypothalamus, the pituitary, or the gonads (ovary or testis)
5. The target organs for hormones discussed in this class are the pituitary, the gonads, or other organs
6. In many cases, the target of a hormone produces another hormone that acts on another target, and so on.
7. In response to binding a hormone, the target cell responds dividing, synthesizing a molecule, or differentiating (changing)
Early Embryonic Development of the Reproductive Tract
1. Sex chromosomes: XX (female) or Xy (male)
2. At 5-6 weeks postconception, the reproductive tract is undifferentiated (the same in males and females)
3. If the y chromosome is present at 6 1/2 weeks postconception, the undifferentiated gonad becomes a testis, under the influence of testis determining factor (genetic code on y chromosome)
4. If the gonad is a testis, it begins to produce testosterone, which causes further development in the direction of male structures
5. If there is no y chromosome, there is no TDF, and the undifferentiated gonad becomes an ovary
6. If the gonad is an ovary, no testosterone is produced, and the structures develop in the direction of the female
7. By 10 weeks postconception, the internal reproductive structures are clearly differentiated.
8. By 12 weeks postconception, the external reproductive structures are fully differentiated.
9. See handout for names of male and female structures that differentiate from the same undifferentiated embryonic structure.
10. Vocabulary: Testis, ovary, TDF, Mullerian ducts, Wolffian ducts, Fallopian tubes, uterus, vagina, MDIF, labioscrotal swellings, penis, scrotum, labia, epididymis, vas deferens, glans of penis, glans of clitoris, raphe and body of penis, etc.
Abnormalities of Development of the Reproductive Tract
1. Pseudohermaphrodites: incomplete differentiation of genital structures
2. Adrenogenital syndrome
  1. Person is XX, a genetic female
  2. Since there is no y chromosome, the gonad becomes an ovary in the fetus
  3. The adrenal glands produce too much testosterone at the wrong time
  4. This leads to masculinization of the internal and external reproductive structures
  5. Nonfunctional ovary, no vaginal opening, fused labia, clitoris enlarged
3. Progestin-induced masculinization
  1. Person is XX, a genetic female
  2. Mother was given progestins during pregnancy to prevent miscarriage
  3. Depending on timing, duration of treatment, etc., results in masculinization of reproductive structures
4. Androgen insensitivity syndrome
  1. Person is Xy, a genetic male
  2. Since there is a y chromosome, the gonad becomes a testis and begins to produced testosterone normally
  3. However, the target organs that should respond in the presence of testosterone fail to detect it
  4. The target organs may have no receptors, or have defective receptors, but they remain insensitive to testosterone
  5. Reproductive structures are femininized, leading to development of incompletely male structures
  6. Small penis, internal tubes abnormal, etc.
Hormones during Puberty
1. Process, second period of sexual differentiation initiated by increase in sex hormone production
2. Differences from embryonic/fetal period
  1. Female sex hormones important in puberty, but not embryo/fetus
  2. No critical time point for hormone action
  3. Hormones needed throughout rest of adult life
  4. Amount of hormone is related to response to hormone (dose response)
  5. Females need a small amount of testosterone (related to sex drive)
  6. Nonreproductive structures are affected by hormones
3. See handout for comparison of pubertal changes in girls and boys
  1. Girls: first sign is growth of breasts; boys: first sign is growth of testes/scrotum
  2. Height growth earlier in girls than boys on average
  3. Menarche: beginning of menstruation
  4. Some changes permanent; others reversible
  5. Normal for changes to occur at different times over range of years
Hormones in the Adult Male
1. Hypothalamus produces releasing factors for luteinizing hormone (LH) and follicle stimulating hormone (FSH)
2. Releasing factors act on pituitary to amke it release LH and FSH
3. FSH and LH are gonadotropins--seek out testis
4. LH acts on interstitial cells in testis to stimulate them to produce testosterone
5. FSH acts on seminiferous tubules to promote sperm production
6. Testosterone promotes maturation of sperm, and has many other effects throughout body
7. Regulation of hormone production is under homeostatic control
8. As testosterone level increases, negative feedback turns off the hypothalamus' production of releasing factors
9. No releasing factors means pituitary stops releasing LH and FSL
10. No FSH/LH means interstitial cells stop producing testosterone and sperm production and maturation slows
11. When level of testosterone falls too low, negative feedback no longer occurs, and hypothalamus resumes production of releasing factors.
12. Homeostatic control keeps hormone levels near a predetermined level (like the set point on a thermostat)
13. Hormone levels in men are very stable over days and months and from year to year
14. Gradual decline after age 20, noticeable from decade to decade--this represents a gradual change in the "set point" for testosterone concentration in the hypothalamus
15. Anabolic steroids: synthetic androgenic hormones
  1. Brain (hypothalamus) perceives a high testosterone level
  2. Reduced pituitary hormone production leads to decrease in natural testosterone level, while artificial testosterone level remains high and may be detected by some tissues
  3. Prolonged exposure to anabolic steroids results in infertility, decreased sex drive, testicular atrophy, breast development
  4. Liver damage may result from its prolonged attempts to detoxify the steroids
  5. Behavioral changes also occur (increased aggression, rage)
  6. Adverse reactions also occur in women who take anabolic steroids regularly
Hormones in the Adult Female
1. Nonpregnant Menstrual Cycle
  1. Two tissues are varying
    1. Ovary varying in structure and hormone production
    2. Uterine lining (endometrium) varying in thickness and structure
  2. Four hormones are varying
    1. FSH, LH (from pituitary)
    2. Estrogen, progesterone (from ovary)
    3. Hormone levels in women vary during each menstrual cycle; peak estrogen level is highest at age 30-35 and declines thereafter.
  3. Hypothalamus produces releasing factors for luteinizing hormone (LH) and follicle stimulating hormone (FSH)
  4. Releasing factors act on pituitary to amke it release LH and FSH
  5. FSH and LH are gonadotropins--seek out ovary
  6. LH acts on ovary, triggers ovulation, development of corpus luteus
  7. FSH acts on ovary, stimulates development of primary follicle in ovary
  8. Developing follicle cells produce estrogen in first half of cycle
  9. Corpus luteum cells begin to produce progesterone in second half of cycle
  10. Both progesterone (P) and estrogen (E)act on uterine lining
    1. In the first half of the cycle, estrogen promotes thickening of the lining, and growth of blood vessels and secretory glands that would support implantation of fertilized egg if there were one (proliferative phase)
    2. In the second half of the cycle, progesterone makes the glands begin to secrete substances that would nourish cells of an implanted zygote if there were one (secretory phase)
  11. Negative feedback from high level of estrogen (and probably progesterone) turns off hypothalamus, resulting in decreased production of LH and FSH by pituitary
  12. Without LH, the corpus luteum degenerates (into corpus albicans, eventually) and stops making E and P
  13. Sharp decrease in E and P triggers separation of uterine lining from its base layer (desquamation), leading to menstruation
  14. During menstruation, uterine lining is lost along with about 70 ml of blood during a 3-7 day period
  15. Refer to handout graph of the female endocrine cycle
  16. Uterine cramps during menstruation are contractions of muscle layer of uterus, due to release of prostaglandins (normal body chemical, make muscle cells contract) when endometrium comes apart from the base layer
  17. Premenstrual syndrome (PMS)
    1. Only 5-10% of women experience severe symptoms, 25% have no symptoms, 50-75% have mild symptoms
    2. Symptoms include worsening of asthma, acne, or herpes, fatigue, fluid retention, headaches, depression, anxiety, irritability
    3. Cause not clear, possibly a change in the E:P ratio over last 3-4 days of cycle
    4. Recent evidence for involvement of brain neurotransmitters, esp. serotonin
    5. No one treatment particularly useful, although modifications of diet and exercise help some women, as does progesterone
    6. More recent treatment designed to increase serotonin levels with drugs like Zoloft have proven effective in many cases
  18. Birth control pills containing estrogen and progesterone provide an outside source of these hormones that causes negative feedback and suppression of ovulation as long as they are present.
2. Early Pregnancy
  1. If there is a fertilized egg (a zygote), the uterine lining must be preserved to continue the pregnancy
  2. Negative feedback from continued high levels of E andP has turned off the hypothalamus (no RF) and the pituitary (no LH/FSH)
  3. When the corpus luteum degenerates, there will no longer be E and P to maintain the uterine lining.
  4. So how can the uterine lining be preserved in the absence of E and P?
  5. Implanted embryonic trophoblast begins to produce embryonic hormone (HCG, human chorionic gonadotropin) very like LH, so that as LH level falls, gradually HCG level rises, preserving the uterine lining
  6. As the pregnancy continues, the hypothalamus, pituitary, and ovary continue to be suppressed by negative feedback from high levels of E and P
  7. Corpus luteum continues to produced E and P (maternal) for the first 10-11 weeks of pregnancy, preserving the uterine lining
3. Later Pregnancy
  1. As trophoblast matures into the placenta (11-12 weeks), it stops making HCG, the corpus luteum degenerates and stops making E and P
  2. As placenta matures, it begins to make E and P (fetal) to replace the maternal E and P no longer being made
  3. During pregnancy, the fetal E and P maintains the utering lining
  4. Estrogen also promotes growth of many materal tissues, strengthening the myometrium, increasing blood flow, promoting growth of blood vessesl, stimulating contractions of uterus
  5. Progesterone prevents uterine contractions, prevents premature expusion of fetus from uterus
  6. Relaxin (may be function of progesterone) softens cervix and loosens pelvic joints in preparation for childbirth
  7. Hormones cause breast changes that prepare for lactation
    1. Human placental lactogen (HPL, fetal)--acts to cause differentiation of milk ducts (become more mature), milk sacs begin to produce colostrum
    2. Estrogen (fetal) promotes duct growth
    3. Progesterone (fetal) promotes growth and function of milk sacs
    4. Prolactin (maternal pituitary hormone) initiates milk production after birth (E suppresses prolactin during pregnancy, but decreases after birth, allowing prolactin to act)
  8. End of pregnancy probably triggered by placental aging, which decreases E and P produced, changing P:E ratio
  9. Production and release of prostaglandins triggers uterine contractions, leading to labor and delivery
  10. Oxytocin (maternal pituitary hormone)
    1. Triggers release of milk from milk sacs (2-3 days after delivery)
    2. Infant suckling stimulates hypothalamus, then pituitary produces oxytocin, which allows release of milk
    3. Oxytocin also stimulates uterine contractions (by causing release of prostaglandins) after delivery, which shrink the uterus, stop blood flow from vessels broken when placenta separated from uterine wall during delivery