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17.16 Additional Effects of Gonadal Steroids- estrogen
- Estrogen has other effects in addition to its paracrine function within the ovaries, its effects on the anterior pituitary gland and the hypothalamus, and its uterine actions. They are summarized in Table 17.8.
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Additional effects of gonadal steroids- progesterone
- Progesterone also exerts a variety of effects (also shown in Table 17.8). Because the plasma progesterone concentration is markedly increased only after ovulation has occurred, several of these effects can be used to indicate whether ovulation has taken place.
- First, progesterone inhibits proliferation of the cells lining the vagina.
- Second, there is a small increase (approximately 0.5°C) in body temperature that usually occurs after ovulation and persists throughout the luteal phase; this change is probably due to an action of progesterone on temperature regulatory centers in the brain.
- Note that in its myometrial and vaginal effects, as well as several others listed in Table 17.8, progesterone exerts an “antiestrogen effect,” probably by decreasing the number of estrogen receptors.
- In contrast, the synthesis of progesterone receptors is stimulated by estrogen in many tissues (for example, the endometrium), and so responsiveness to progesterone usually requires the presence of estrogen (estrogen priming).
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Estrogen priming
- Note that in its myometrial and vaginal effects, as well as several others listed in Table 17.8, progesterone exerts an “antiestrogen effect,” probably by decreasing the number of estrogen receptors.
- In contrast, the synthesis of progesterone receptors is stimulated by estrogen in many tissues (for example, the endometrium), and so responsiveness to progesterone usually requires the presence of estrogen (estrogen priming).
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Premenstrual tension, premenstrual syndrome (PMS), or premenstrual dysphoric disorder (PMDD)
- Transient physical and emotional symptoms that appear in many women prior to the onset of menstrual flow and disappear within a few days after the start of menstruation.
- The symptoms— which may include painful or swollen breasts; headache; backache; depression; anxiety; irritability; and other physical, emotional, and behavioral changes—are often attributed to estrogen or progesterone excess.
- The plasma concentrations of these hormones, however, are usually normal in women having these symptoms, and the cause of the symptoms is not actually known.
- In order of increasing severity of symptoms, the overall problem is categorized as premenstrual tension, premenstrual syndrome (PMS), or premenstrual dysphoric disorder (PMDD), the last-named being so severe as to be temporarily disabling.
- These symptoms appear to result from a complex interplay between the sex steroids and brain neurotransmitters.
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Additional effects of gonadal steroids- androgens
- Androgens are present in the blood of women as a result of production by the adrenal glands and ovaries (see Figure 17.6).
- These androgens have several important functions in the female, including stimulation of the growth of pubic hair, axillary hair, and, possibly, skeletal muscle, and maintenance of sex drive.
- Excess androgens may cause virilization: The female fat distribution lessens, a beard appears along with the male body hair distribution, the voice lowers in pitch, the skeletal muscle mass increases, the clitoris enlarges, and the breasts diminish in size.
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17.17 Puberty
- Puberty in females is a process similar to that in males.
- It usually starts earlier in girls (10 to 12 years old) than in boys.
- In the female, GnRH, the gonadotropins, and estrogen are all secreted at very low rates during childhood. For this reason, there is no follicle maturation beyond the early antral stage and menstrual cycles do not occur. The female accessory sex organs remain small and nonfunctional, and there are minimal secondary sex characteristics.
- The onset of puberty is caused, in large part, by an alteration in brain function that increases the secretion of GnRH.
- It is currently thought that activation of kisspeptin neurons in the hypothalamus is involved in the increase in GnRH that occurs early in puberty. GnRH in turn stimulates the secretion of pituitary gland gonadotropins, which stimulate follicle development and estrogen secretion.
- Estrogen, in addition to its critical role in follicle development, induces the changes in the accessory sex organs and secondary sex characteristics associated with puberty
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Menarche
Menarche, the first menstruation, is a late event of puberty (averaging about 12.5 years of age in the United States).
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The mechanism of the brain change that results in increased GnRH secretion in girls at puberty
- As in males, the mechanism of the brain change that results in increased GnRH secretion in girls at puberty is not certain.
- The brain may become less sensitive to the negative feedback effects of gonadal hormones at the time of puberty.
- Also, the adipose-tissue hormone leptin (see Chapter 16) is known to stimulate the secretion of GnRH and may contribute to the onset of puberty.
- This may explain why the onset of puberty tends to correlate with the attainment of a certain level of energy stores (fat) in the girl’s body.
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Amenorrhea
- The failure to have menstrual flow (menses) is called amenorrhea.
- Primary amenorrhea is the failure to begin normal menstrual cycles at puberty (menarche), whereas
- Secondary amenorrhea is defined as the loss of previously normal menstrual cycles.
- As we will see, the most common causes of secondary amenorrhea are pregnancy and menopause.
- Excessive exercise and anorexia nervosa (self-imposed starvation) can cause primary or secondary amenorrhea.
- There are a variety of theories for why this is so.
- One unifying theory is that the brain can sense a loss of body fat, possibly via decreased concentrations of the hormone leptin, and that this leads the hypothalamus to cease GnRH pulses.
- From a teleological view, this makes sense because pregnant women must supply a large caloric input to the developing fetus and a lack of body fat would indicate inadequate energy stores.
- The prepubertal appearance of adolescent female athletes with minimal body fat may indicate hypogonadism and probably amenorrhea, which can persist for many years after menarche would normally take place.
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Onset of puberty
- The onset of puberty in both sexes is not abrupt but develops over several years, as evidenced by slowly increasing plasma concentrations of the gonadotropins and testosterone or estrogen.
- The age of the normal onset of puberty is controversial, although it is
- generally thought that pubertal onset before the age of 6 to 7 in girls and 8 to 9 in boys warrants clinical investigation.
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Precocious puberty
- Precocious puberty is defined as the very premature appearance of secondary
- sex characteristics and is usually caused by an early increase
- in gonadal steroid production.
- This leads to an early onset of the puberty growth spurt, maturation of the skeleton, breast development (in girls), and enlargement of the genitalia (in boys).
- Therefore, these children are usually taller at an early age.
- However, because gonadal steroids also stop the pubertal growth spurt by inducing epiphyseal closure, final adult height is usually less than predicted. Although there are a variety of causes for the premature increase in gonadal steroids, true (or complete) precocious puberty is caused by the premature activation of GnRH and LH and FSH secretion.
- This is often caused by tumors or infections in the area of the central nervous system that controls GnRH release.
- Treatments that decrease LH and FSH release are important to allow normal development
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17.18 Female Sexual Response
- The female response to sexual intercourse is characterized by marked increases in blood flow and muscular contraction in many areas of the body. For example, increasing sexual excitement is associated with vascular engorgement of the breasts and erection of the nipples, resulting from contraction of smooth muscle fibers in them.
- The clitoris, which has a rich supply of sensory nerve endings, increases in diameter and length as a result of increased blood flow.
- During intercourse, the blood flow to the vagina increases and the vaginal epithelium is lubricated by mucus.
- Orgasm in the female, as in the male, is accompanied by pleasurable feelings and many physical events. There is a sudden increase in skeletal muscle activity involving almost all parts of the body; the heart rate and blood pressure increase, and there is a transient rhythmic contraction of the vagina and uterus.
- Orgasm seems to have a minimal function in ensuring fertilization because
- fertilization can occur in the absence of an orgasm.
- Sexual desire in women is probably more dependent upon androgens, secreted by the adrenal glands and ovaries, than estrogen.
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17.19 Menopause
- When a woman is around the age of 48 to 55 years, menstrual cycles become less regular.
- The phase of life during which menstrual irregularity begins is termed perimenopause.
- Ultimately, menstrual cycles cease entirely in all women; when this period exceeds 12 months, this cessation is known as menopause.
- The cessation of reproductive function involves many physical and
- sometimes psychological changes.
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Menopause causes
- Menopause and the irregular function leading to it are caused primarily by ovarian failure.
- The ovaries lose their ability to respond to the gonadotropins, mainly because most, if not all, ovarian follicles and eggs have disappeared by this time through atresia.
- The hypothalamus and anterior pituitary gland continue to function relatively normally as demonstrated by the fact that the gonadotropins are secreted in greater amounts.
- The main reason for this is that the decrease in the plasma concentrations of estrogen and inhibin result in less negative feedback inhibition of gonadotropin secretion.
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Menopause symptoms
- A small amount of estrogen usually persists in plasma beyond menopause, mainly from the peripheral conversion of adrenal androgens to estrogen by aromatase, but the concentration is inadequate to maintain estrogen dependent tissues.
- The breasts and genital organs gradually atrophy.
- Thinning and dryness of the vaginal epithelium can cause sexual intercourse to be painful.
- Because estrogen is a potent bone-protective hormone, significant decreases in bone mass may occur (osteoporosis).
- This results in an increased risk of bone fractures in postmenopausal women.
- The hot flashes so typical of menopause are periodic sudden feelings of warmth, dilation of the skin arterioles, and marked sweating.
- The effects of estrogen in the temperature-regulating regions of the hypothalamus are thought to be at least partially responsible for hot flashes. In addition, the incidence of cardiovascular disease increases after menopause.
- Many of the symptoms associated with menopause, as well as the development of osteoporosis, can be reduced by the administration of estrogen.
- The desirability of administering estrogen to postmenopausal women is controversial, however, because estrogen administration increases the risk of developing uterine endometrial cancer and breast cancer.
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