1. Hormones Produced by the Testicle:

     The testicles, which produce sperm cells, also produce a hormone which accounts for many of the differences between the sexes; in the same way, the female hormones, produced by the ovaries, bring about the difference between the "intersex" type and the normal woman. Such intersex persons develop when the gonads are removed early in life. Some differences still exist, but these are probably due to production of the hormones before birth. >Transvestism and homosexuality are usually more psychological than physiological disorders, and they will not be considered in this book beyond these statements: persons with any of these conditions usually find it more comfortable to attribute their deviations to gonadal abnormalities than to psychological factors. In some cultures they are encouraged: the Greece of Socrates was one of them, and our own may be another.

     The origin of the word testicle is interesting. The Latin word for witness is testis, and its diminutive form is testiculus, so a Roman taking an oath would swear by his testiculi, his "little witnesses".

     The microscopic structure of the testis shows its double function. The production of sperm cells occurs in the seminiferous tubules. In section, these are circular and hollow at the center, which is the conduit for the spermatozoa. The circles do not touch each other, and the space between them is filled with the interstitial cells, which are the source of the male hormone. A section of the testicle is shown in Figure 364. The production of semen will be considered in Chapter 27.

     The testicular hormone is called testosterone. It is a steroid hormone (Figure 365) which exerts profound effects on the body. Muscular development is enhanced along with bone growth, and the prostate gland and seminal vesicles grow, as do the penis and scrotum. The growth of facial hair is stimulated; body hair, especially pubic hair, becomes thicker, and the hair of the scalp recedes. Growth of the larynx changes the voice. The effect on muscular development is not culturally determined, for it seems a general rule among mammals that the male animal is larger and more muscular than the female, though in most mammals, including humans, the female does more work.

     Testosterone production is under pituitary control; the hormone is identical with a pituitary hormone present in both sexes, called luteinizing hormone. The production of the latter is under testosterone control; as testosterone production falls, so does luteinizing hormone production. This relationship will be considered again in Part 4 of this chapter. It is possible, but not proved, that the same type of relationship exists for the production of spermatozoa; the pituitary hormone being a different one (Part 4). There is strong evidence that testosterone also acts on the seminiferous tubules.

2. Hormones Produced by the Ovary:

     Two hormones are produced by the ovary. One, produced in connection with the development of the egg cell, or ovum, is called estrogen; the other, produced by the tissue which fills in the space occupied by the ovum after its discharge, is called progesterone. Actually there are at least three hormones in the "estrogen" group, but one of them predominates in both quantity and effect.

     The anterior lobe of the pituitary, through luteinizing hormone, stimulates the production of estrogen, which in turn suppresses the production of lutinizing hormone. The student should note the similarity of the sexes in this respect. The production of progesterone suppresses pituitary production of follicle stimulating hormone from the pituitary. This relationship is a well established one, unlike the male relationship (See Part 5).

     Oddly, the ovary can also produce a weak male hormone, androsterone rather than testosterone, but it does so to a very small extent in the normal woman during her reproductive years.

     Just as the male hormone produces characteristic body changes in the male, the female hormones do so in the female. The growth of the breasts depends on the female hormones. Most of the other changes seen in the female depend on the absence of male hormone rather than the presence of female hormones. For example, the voice does not change, muscular development is not exaggerated, the disappearance of childhood fat from some locations does not occur, and the face and body do not become hairy. Neither does the hairline recede.

     A few of the body changes which occur in adult females are due to small amounts of male hormone; some from the ovary, some from the adrenal cortex (See Part 9).

     The similarities between male and female hormones, shown in Figure 366, are impressive. Testosterone differs from the principal estrogen by having one extra hydrogen, while it differs from progesterone by having two extra hydrogens and two extra carbons.

     It has often been suggested that female animals are more nearly typical of the species than male, the secondary sexual characteristics of males being, as it were, tacked on to the "basic" animal type.

3. Male Hormonal Inter-Relationships:

     The hormonal interrelationships in a male are quite simple. Testosterone produced in the interstitial cells acts to inhibit the production of the luteinizing hormone of the pituitary, so that testosterone production is turned off, leading to new secretions of the luteinizing hormone.

     The seminiferous tubules, secreting under the control of follicle stimulating hormone from the anterior pituitary, turn it off (the mechanism is quite unknown). Free from this suppression, follicle stimulating hormone is released again.

     In the end, both testosterone production and sperm production are produced at a steady rate. It seems probable, however, that the levels of production are "set" in the hypothalamus. A physical model may clarify this: A car, in gear, coasting down hill is accelerated by gravity, but decelerated by frictional losses in the moving parts of the engine. Although pushing the car, in either direction, may change its rate momentarily, it will find its normal rate again after the pushing is stopped. On the other hand, changing the gear changes the speed at which the car coasts.

     Presumably, the hypothalamus "changes the gears", making the pituitary more or less responsive to the "push" from the testicular secretions.

     These relationships are shown diagrammatically in Figure 367. This Figure also shows the "releasing hormones" through which the hypothalamus is presumed to act on the pituitary. See also Part 7.

4. Sexual Development:

     Whether a male or female develops from a fertilized egg depends on the chromosomes contributed by the sperm, a brief description follows.

     The body cells of males contain chromosomes which are confined to the cell nucleus. These are almost identical in male and female animals, but not quite so. For example, 22 of the 23 pairs of chromosomes in women are just like those of men. The twenty third pair in women consists of two chromosomes similar to each other; in men, the twenty third pair consists of one chromosome like a member of the twenty third female pair, and one which is smaller. The small one is called the Y; the large is called the X.

     The formation of germ cells in both sexes involves a splitting of the pairs. In women, obviously, each germ cell, derived from a cell with two X chromosomes, produces two half cells (haploid), each with an X chromosome. In men, splitting results in two slightly dissimilar cells, one contains an X, one a Y chromosome. It may be worth mentioning that modern physical and physio-chemical techniques may make possible the separation of sperm cells containing X from those with Y chromosomes. The consequences of this will be seen in a moment.

     A haploid sperm cell containing an X chromosome, fertilizing a haploid egg cell which always contains the X chromosome, results in the formation of an XX cell, a female cell. Conversely, fertilization by a sperm cell containing the Y chromosome results in an XY cell, a male.

     Chromosomes contain genes, large paired molecules which have the extraordinary ability to separate from their partners. Each separate partner can synthesize a partner just like the original one. Thus chromosomes are virtually self-duplicating.

     Furthermore, the genes have the ability to give instructions to the rest of the cell, so far as protein synthesis is concerned. Some of the proteins are enzymes, and some dictate the course of development by means as yet unknown. The cells developing from the union of sperm and egg contain genes from both parents; their enzyme content is rather like that of both parents, and so is their development.

     This extends even to sexual development. The early embryo is bisexual. If the Y chromosome is present, the primitive genital tract becomes modified, probably by endocrine secretions of the primitive gonad, to a male type of development. The XX combination leads to female development.

     At birth, most babies show their sex only in the genital area. Until adolescence, boys and girls are not really different, except genitally. What differences there are are most likely imposed by the culture. The hypothalamis is sexually quite inactive; so are the gonads. The embryonic genitalia and their differentiation into male and female are shown in Figure 368.

5. Adolescence in the Male:

     The indifferent stage lasts in both sexes until sometime in the teens, although there are innumerable case of earlier and later adolescence. It appears to be associated with hypothalamic stimulation of the pituitary and the consequent gonadal release of testosterone.

     The growth of facial and body hair, the deepening of the voice, increased body height and weight (due mostly to muscle) and growth of the penis, prostate, and seminal vesicles occur over a period of five years or so, but there is no particular order in which these events occur. Along with these, there develops a strong interest in girls and sexual activity.

6. Adolescence in the Female:

     Adolescence in the female usually begins with the secretion of ovarian hormones under the influence of the pituitary, which is in turn controlled by the hypothalamus. The uterus and vagina begin to grow, as do the breasts. Menstruation comes somewhat later.

     It is customary to refer to the period which occurs in girls after the onset of sexual change but before menstruation as puberty. The same term applied to boys is confusing, since there is no clear cut sign of sexual maturity in them.

     The appearance of menstrual bleeding in girls marks the beginning of the menarche, which will be terminated by the menopause 30-40 years later. Menstruation is seen in primates only. Other female animals have vaginal bleeding, but it is related to "heat" or estrus, and corresponds to the period when the female is most receptive to the male and most likely to be fertilized. Quite the opposite is true during the human menstrual period.

     The hormonal changes that occur during the menstrual cycle are such as to enhance female development; after a few menstrual cycles, this development is quite complete. When pregnancy occurs, the hormones of pregnancy add their effects to those of the gonads.

7. The Menstrual Cycle:

     The menstrual cycle is quite complex, involving the ovaries, pituitary, uterus, and breasts. Some aspects of it are not yet fully understood. A brief summary may orient the student to the more detailed account which follows:

     The menstrual cycle is considered to begin on the first day of vaginal bleeding. The fluid lost contains blood, and most of the lining of the uterus, endometrium, built up since the last bleeding. After bleeding stops, the ovaries, driven by the pituitary, bring an egg cell to maturity at the same time produce a hormone which causes endometrial build-up to begin and progress. About half way through the cycle, the ovum is released; the ovary produces a new hormone (again under pituitary influence) which together with the old ovarian hormone further changes the endometrium so that it becomes suited for implantation of the fertilized ovum. If fertilization fails, so do the two ovarian hormones. The endometrium, overgrown and over-prepared, is dependent on an adequate blood supply, but this too is dependent on the ovarian hormones. The blood vessels close off, the dying endometrium is shed into the uterine cavity, and the dead material, along with some blood from blood vessels not quite closed, makes the menstrual flow.

     There are many misconceptions about the menstrual cycle. Some believe that the menstrual discharge represents a great deal of blood, though it actually contains some thing like 30 ml, equivalent to the amount of blood destroyed in 12 hours by an 80 kg man. The popular idea that the cycle is 28 days long should be classed with the idea that it is regular. Both are notable for the frequency of the exceptions. Likewise, the idea that the ovum is released and conception is possible on the fourteenth day, or half way through the cycle, is a very rough approximation. Conception can occur at any time in the cycle.

     Perhaps the most pernicious of the popular misconceptions has to do with the idea that menstrual cycles are related to femininity. Women after menopause, or after removal of the ovaries, often become despondent over the fact that they are no longer sexually attractive, behaving accordingly, they find their notions reinforced, a good example of a self-fulfilling prophecy.

     At the beginning of the normal menstrual cycle, the ovary is relatively quiescent and the endometrium very thin. The pituitary, unchecked by ovarian hormones, releases follicle stimulating hormone, the same hormone which stimulates the seminiferous tubules in the male. It appears to do so through the hypothalamus, which secretes a polypepticle hormone, called follicle stimulating releasing factor.

     The resting ovary contains egg cells derived from its outside layer, the germinal epithelium. These cells are surrounded by secretory cells. Under the influence of follicle stimulating hormone, one of these (usually only one, but not always) primordial follicles is stimulated to secrete a fluid called the follicular liquor. This fluid is rich in estrogenic hormones, which have two effects: they cause the endometrium to begin its growth again and they cause partial suppression of the follicle stimulating hormone.

     The follicle continues to grow; the ovum, on a stalk of-the secretory cells, becomes more mobile. The outside of the follicle reaches the outside of the ovary and the follicle ruptures. The modile ovum literally falls out through the ruptured area, usually into the oviduct, called the Fallopian tube in woman, and from there it proceeds to the cavity of the uterus.

     The female reproductive organs are shown in Figure 369. The maturation of the follicle is shown in Figure 370.

     It will be recalled that the suppression of the follicle stimulating hormone by follicular estrogen was incomplete. At the time of that suppression, the pituitary suddenly produces large amounts of the luteinizing hormone. Like follicle stimulating hormone, luteinizing hormone is under hypothalamic control; the control is exerted through a polypeptide hormone, luteinizing releasing hormone. It appears as if suppression of pituitary synthesis of follicle stimulating hormone redirects its activities so that the luteinizing hormones is produced instead. In males, the luteinizing hormone stimulates the production of testosterone via the interstitial cells of the testis. In females, the follicular space is quite suddenly filled with a group of yellow-looking endocrine cells, the corpus luteum. These cells produce progesterone, which like estrogen has two effects: in conjunction with estrogen, which is also produced by the corpus luteum, the endometrium is thickened further and caused to secrete materials, primarily glycogen, which are highly nutritive. The second effect is to turn off pituitary production of luteinizing hormone with dramatic suddenness.

     The corpus luteum remains, however; its production of both progesterone and estrogen increases for about a week. Eventually, the production of both luteinizing hormone and follicle stimulating hormone is turned off; the corpus luteum, no longer supported by the pituitary, disappears, and the endometrium, no longer supported by estrogen and progesterone, is shed as described before, and the next cycle begins.

     These relationships are summarized in Figure 371. In studying this Figure, the student should remember the following:

(1) The timing shown is inexact. The Figure approximates the behavior of a group not of any one person.

(2) The blood levels of luteinizing hormone, progesterone, and estrogen have been measured. The behavior of the follicle stimulating hormone is deduced, but not measured.

(3) Follicle stimulating hormone probably helps maintain the life of the corpus luteum. The combined level of progesterone and estrogen produced by the corpus luteum is probably the "turn off" signal for the production of follicle stimulating hormone.

(4) Hypothalamic control is of the greatest significance. It has been suggested that the hypothalamus affects the pituitary through releasing hormones, one for luteinizing hormone, and one for follicle stimulating hormone. These so-called neural hormones are believed to be polypeptides, but they have not been isolated, so they are shown in the figure in brackets. It cannot, however, be denied that the hypothalamus controls the pituitary hormones by some means. The most impressive example of this is seen in rabbits, where ovulation occurs only after copulation, and within a few hours. It seems probable that this response involves the hypothalamus acting on the pituitary, which is stimulated to release follicle stimulating hormone. The interesting possibility that exceptionally fertile women respond in the same way as rabbits may tend to diminish the effectiveness of birth control methods which, depend on abstention from sexual relationships during the presumed period of ovulation.

     A pituitary hormone separate from the follicle stimulating hormone which maintains the life of the corpus luteum has been shown to be effective in rats. It has not been shown to be effective in humans, and is therefore omitted from the Figure. This hormone has another role (it is concerned with milk production in humans). It will be discussed in Chapter 28 and 29.

     Although changes in the breasts occurring during the cycle are not shown in the Figure, they are of considerable importance subjectively. The breasts are glandular structures, capable of producing milk from blood in the right hormonal circumstances. These will be discussed in Chapters 28 and 29. For the moment, it should be noted that the glandular tissue of the breasts responds to both estrogen and progesterone by hypertrophy and secretion. There is a distinct enlargement of the breasts during the menstrual cycle; the normal condition is restored during menstruation, when the stimulating hormones are absent.

     Many women experience a sharp pain in the abdomen at the time of ovulation, called mittelschmerz, which lasts for only a few hours. In German, this means "middle (of cycle) pain". Other women become nervous and uneasy just before menstruation. This premenstrual tension is usually associated with the retention of salt and water; estrogens have a weak aldosterone effect. Premenstrual tension may also result from pain in distended breasts.

     Body temperature changes in the menstrual cycle used to be favored as a guide for the determination of the time of ovulation. A slight 1⁰F rise occurs with ovulation and is sustained through the cycle until just before the next menstruation. The measurement is virtually useless when it is used to indicate the favorable time for conception, since the temperature does not show an unmistakable elevation for two or three days. By this time the egg is no longer fertile.

     Unusual delay in a menstrual period may be due to hypothyroidism, hyperthyroidism, nervousness, anxiety, change in climate, illness, and a variety of other factors. The fact that these factors may delay the time of menstruation should not be taken to indicate that they are the usual cause. Almost invariably, delayed menstruation in a woman who has had sexual relations with a man signifies pregnancy, whether or not that pregnancy is desired. This fact, usually accepted by most people with good sense, seems to come as a surprise to most college students.

     The hormonal changes of pregnancy will be discussed in Chapters 28 and 29.

8. Sexual Hormones of the Adrenal:

     The adrenal cortex secretes a hormone with testosterone-like activity and another with estrogenic activity. The testosterone-like hormone is rather weak compared to testosterone itself, while the estrogenic hormone is probably identical with that of the ovary. These hormones are normally of little importance, but when excessive quantities of one or the other are secreted, as in adrenal diseases, they can produce a variety of bizarre, usually, unpleasant effects (See Part 9).

9. Diseases of Sexual Hormones:

     The testicle usually produces normal amounts of spermatozoa and testosterone. Abnormal sexual behavior is more often of psychological than physiological origin. Very rarely, the pituitary overdrives the testicle, but more commonly it underdrives it. In the first case, sexual maturity is achieved early, while in the second, there may be underdevelopment of both testicles and male sex characteristics. The latter condition leads to eunuchoidism if it occurs in early life.

     True eunuchs are produced by early castration, a common procedure in farm animals, and a procedure once practiced on a fairly large scale in boys. Boys so treated grow quite tall--the reason is similar to that involved in the great height of pituitary giants--their voices do not change, their genital organs remain infantile, and their interest in sex is also minimal. They usually lack body hair and show muscular underdevelopment.

     Such boys were often made deliberately to be harem guards; others were made to preserve the soprano voice of young boys--these were the "castratti" of Italy, whose singing voices are said to have been more beautiful than those of the greatest female sopranos.

     Castration in later life does not produce eunuchs nor even abolish the sex drive, though it does diminish it. It is often carried out for the treatment of cancer, particularly cancer of the prostate gland.

     In the hope of increasing sexual activity in later life, the seminiferous tubules have been destroyed, usually by tying their duct, the vas deferens. This operation is quite successful in destroying the seminiferous tubules, and the interstitial cells function exactly as they did before the operation. The student should be able to reason out why.

     Abnormal ovarian function does not usually occur in women during the menarche unless the ovaries are destroyed by disease. Irregular menstrual cycles, menstrual cycles without ovulation, painful menstruation, and excessive or minimal bleeding may all occur, but they do not seem to change either the body structure or the sex drive.

     Some ovarian tumors occurring at an early age may result in precocious puberty, but they are extremely rare. Other ovarian tumors may necessitate removal of the ovaries; in children this requires replacement therapy at the time of adolescence. In adults, removal of the ovaries is of very little physiological consequence, though the psychological effects may be devastating.

     When it is recognized that the menarche may begin over a wide range of years, that the periods are irregular in most women and often do not average 28 days that the bleeding during menstruation is extremely variable, and that it may or may not be associated with pain, one wonders how any pattern of menstruation can be considered abnormal.

     There is, however, an abnormal pattern of menstruation induced deliberately by the administration of ovarian hormones, usually synthetic ones. Such administration results in pituitary suppression, while follicle stimulating hormone in particular is suppressed. The consequence is the failure of the ovary to bring an ovum to maturity, and such women are made temporarily sterile. The hormone used is a synthetic estrogen, and the addition of a little progesterone causes normal endometrial growth. Removal of both hormones produces menstruation. The hormone mixture is the famous "pill", probably the most widely used contraceptive of our time. The only known ill effect of the pill is its tendency to cause blood clotting by an unknown mechanism, but this is rare.

     Excessive production of estrogenic hormones by the adrenal has surprisingly little effect in men and no observable effects in women. When male hormones are produced in men, the effect is not noticeable. In women, particularly women after menopause, the male hormone of the adrenal may lead to the development of male characteristics, especially the growth of body hair, shrinking of the breasts, and the enlargement of the clitoris.

     In children before adolescence, the effects are more serious. Precocious puberty may result in a child being sexually mature as early as 4 years.

     An excessive production of adrenal hormones in early prenatal life, before sexual differentiation has occurred, may lead to masculine development in a person with ovaries or feminization of a person with testicles. The first is much more common. The proper sex of these people is not recognized at birth, and they are brought up according to their sexual appearance. When the true sex is discovered, the characteristics of the sex can sometimes be restored by surgery, but in general, the results are only fair.

     One cannot close without mentioning that surgical alteration of sex is possible in persons whose difficulty is psychological rather than endocrine. It is easier to do this in men who prefer to be women than the other way around. Medical tolerance may be going too far, and it is not clear what is gained by this procedure besides publicity; nevertheless, it is coming to be condemned more and more.

Continue to Chapter 27.