In mammals, the reproductive hormones are more for a preservation of species, not preservation of an individual. In this lecture, we will consider the following definitions of sex: Chromosomal sex is the chromosomal configuration (XX or XY) of an individual; Gonadal sex is whether or not the gonads are testis or ovaries; Phenotypic sex is whether an individual is a boy or girl. Development of the Male Reproductive System—The testes are the male reproductive organs that are responsible for two main functions: the production of testosterone and the production of sperm. During fetal development, the gonads begin to differentiate from indifferent gonadal tissue. In the male, there is a SRY gene present on the Y chromosome. It is responsible for the release of an SRY antigen which stimulates the development of the indifferent gonadal tissue into the testis. The testis have two distinct cell types. The Sertoli cells are found within the seminiferous tubules of the developing testis. They produce Mullerian inhibiting substance/hormone (MIS or MIH) which causes the Mullerian ducts to regress. The Mullerian duct is the gonadal tissue that will develop into a uterus, uterine tubes, and the upper part of the vagina in females. The Leydig cells (AKA interstitial cells) are found outside of the developing seminiferous tubules. They produce testosterone which promotes the transformation of the Wolffian ducts into the epididymis, vas deferens, and seminal vesicles. Testosterone is also converted into dihydrotestosterone(DHT) in certain tissues by the enzyme 5-α-reductase. DHT is responsible for the development of the external male genitalia. If an individual is deficient in 5-α-reductase, this can lead to ambiguous external genitalia. This type of condition is seen in males in the Dominican Republic. They are raised as females, but during puberty, there is heavy gonadotropin influence which can lead to the development to male external genitalia. Testicular Descent—The testis are formed within the male abdominal cavity. However, this is not a favorable environment for spermatogenesis to occur because the core body temperature is too high for this process to occur. The testis will descend to the scrotal sac outside of the body. First there will be trans-abdominal movement of the testis. Then, each one will descend through the inguinal canal to reach the scrotal sac. The development and descent of the testis takes the entire gestational period. In some males, the testis has not fully descended at birth on one or both sides. This condition is called cryptorchidism. It may be due to mechanical problems, such as the inguinal canal closing prematurely. This must be corrected by surgery. It may also be due to some form of hormonal deficiency. In either case, the descent of the testis is
recommended, because an abnormal testicular location is a source of malignancy and also creates infertility problems. The temperature within the scrotal sac is maintained by the cremasteric muscle. This muscle can contract or relax to raise the testis in response to the environmental temperature. The pampiniform venous plexus is also involved in the regulation of temperature of the testis. If there is an increase in temperature of the testis (for example, due to febrile infection or extremely hot environmental conditions), sperm production can be inhibited/shut off. Cells of the Testis—The testis contains spermatogonia and Sertoli cells within the seminiferous tubules and Leydig cells (interstitial cells) on the periphery. The spermatogonia are the stem cells within the seminiferous tubules. They create a spermatogenic wave; that is, there is a continual production of mature sperm. This process takes 60-70 days. The Sertoli cells are the source of Mullerian Inhibiting Substance. This controls testicular descent and Mullerian duct degeneration in males. The Sertoli cells provide a structural attachment for normal seminiferous tubule production. They also are responsible for the nourishment of the spermatogonia. The Leydig cells produce testosterone. It has many effects on the reproductive system and throughout the body and will be described below. Sertoli Cell Functions—The Sertoli cells form the blood-testis barrier. The Sertoli cells are joined by gap junctions. These barriers separate the spermatogonia from the spermatocytes. It also protects the developing cells from potentially toxic circulating elements in the blood and also prevents the developing cells from entering the circulation and causing autoimmune destruction of the testis. Steroids such as testosterone can enter through this barrier. This is important b/c the completion of spermatogenesis requires testosterone. The Sertoli cells also secrete androgen binding protein (ABP). ABP is responsible for bringing in testosterone and maintaining it in a high concentration on the luminal side of the tubules. This is necessary for sperm maturation, the completion of spermatogenesis. The Sertoli cells produce aromatase-E2, an enzyme that converts androgens to estrogen. Tumors of the Sertoli cell are often associated with high levels of estrogen. This causes feminization b/c of the high levels. Sertoli cells produce a watery bicarbonate secretion. This secretion contains steroid hormones, potassium, and amino acids and produces an osmotic gradient that aids in the transport of spermatids to the epididymis where final maturation occurs. The Sertoli cells also possess FSH and androgen receptors. The binding of FSH and androgens to these receptors is responsible for the stimulation of spermiogenesis.
The Sertoli cells also function in the regulation of seminiferous tubule metabolism and provides nourishment for the developing sperm. They also produce growth factors for the Leydig cells. Finally, the Sertoli cells secrete Inhibin and Mullerian Inhibiting Substance. Inhibin is a protein that inhibits FSH production. The function of MIS is described above. Hormonal Regulation of the Testis—The hypothalamus releases Gonadatrophin releasing hormone (GnRH) in a pulsatile manner. GnRH is sent to the anterior pituitary where it stimulates the pulsatile release of gonadotropins, FSH and LH. FSH targets the Sertoli cells and binds to specific cell surface receptors here. It initiates spermatogenesis and also stimulates the Sertoli cell to produce inhibin. The inhibin protein feeds back on the anterior pituitary to regulate FSH production there. LH targets the Leydig cells to produce testosterone. It interacts with cell surface receptors on the Leydig cells to stimulate the production of cAMP. This in turn, stimulates the secretion of testosterone. Testosterone initiates a response in the reproductive tract and other body organs. It also travels to the Sertoli cells to promote the completion of spermatogenesis. Finally, testosterone feeds back on the anterior pituitary to control LH secretion and on the hypothalamus to inhibit GnRH release. Testosterone and Transcriptional control—Testosterone binds to receptors within the nucleus of the Sertoli cells to initiate transcriptional activity. It shares the same nuclear receptor with DHT, but DHT has a greater affinity for the receptor and elicits greater transcriptional activity. Within the Sertoli cell, testosterone is converted to estradiol via aromatase activity. The estradiol then exits the cell and travels to enter the Leydig cell where it binds to a nuclear receptor to control transcriptional activity here. (this is not something I really understand, so check this out with someone else if this doesn’t sound legitimate). Testosterone Secretion—Testosterone is secreted by the interstitial cells daily. About 98% is bound to protein and 2% is free. Of the bound testosterone, it is either bound to sex hormone binding globulin or albumin. The amount of plasma testosterone is high during fetal development and then lowers until puberty. At puberty, the level begins increasing again until it levels off in adulthood. By the time a man is older, the levels of plasma testosterone begin to decrease again. The main source of estrogen in males is its peripheral conversion from androgen in adipose tissue. It is thought that as a man ages, the amount of adipose tissue increases. This gives a tendency toward feminization because there is an enhanced production of estrogen. Testosterone Effects—Testosterone has both androgenic and anabolic effects. The androgenic effects are seen on the reproductive tract and accessory structures. These effects include:
Development of external genitalia and accessory glands Development of pubic, axillary, and body hair Enlargement of the larynx and thickening of the vocal cords Loss of hair in the temporal region of the scalp Sperm production Increased libido and potency Growth of facial hair
The anabolic effects are general growth-promoting effects. These include:
Pubertal growth spurt and stoppage of growth
Increased muscle mass (esp. in upper torso)
Positive nitrogen and electrolyte balance (especially enhances sodium and water retention)
Increased RBC production (leads to a tendency of polycythemia, excessive RBC production)
Enlargement of renal and salivary glands
Male sex accessory glands—The epididymis is the primary site of storage and final maturation of sperm. The vas deferens is the tube which carries the sperm from the epididymis to the prostate. The seminal vesicles are responsible for the secretion of about 60& of the semen concentration. They produce prostoglandins which stimulate uterine contractions and enhance sperm motility and penetration of the cervical mucus. The seminal vesicles also produce fructose. It serves as an energy source for the sperm during their transport through the female reproductive tract. The prostate gland secretes about 30% of the total semen concentration. Its secretion is alkaline which aids in neutralizing the acidic female reproductive tract. These secretions also contain a clotting enzyme. The bulbourethral gland also produces an alkaline mucus secretion that serves to neutralize the male urethra prior to ejaculation. The prostate enlarges with aging and can cause compression of the urethra and problems with urinary retention. The secretions of the prostate are testosterone dependent, so it is thought that by treating an enlarged prostate with a drug (ex. Proscar) that decreases DHT levels, the amount of prostate hypertrophy can be decreased. Male Sexual Response—The first phase is the excitatory phase. It involves parasympathetic stimulation resulting in vasodilation within the erectile tissue in the penis. This causes an erection, which is associated with the release of nitric oxide. Nitric
oxide relaxes the smooth muscle of the arteries. The next phase is the ejaculatory phase. This is stimulated by the sympathetic nervous system. In this phase, there is contraction of the accessory sex glands to release semen into the posterior part of the urethra. There is then ejaculation of the semen caused by spasmodic contractions of the erectile tissue of the penis. Erectile dysfunction is a common problem faced by men. One treatment for this is Viagra. As mentioned above, nitric oxide is released during an erection. Nitric oxide stimulates the formation of cGMP. cGMP causes the relaxation of smooth muscle of the arteries, thereby causing the erection. cGMP is broken down by 5-phosphodiesterase. Viagra is a phosphodiesterase inhibitor. It blocks the enzyme and allows cGMP to remain in higher concentrations so the erection can be maintained for longer periods. Fertility Control in Males—Currently there is no male oral contraceptive. Males can be sterilized by a procedure called a vasectomy. A vasectomy involves bilateral ligation of the vas deferens. This procedure can be reversed, but there is a low successive of fertility following this procedure. Pathology associated with the Male Reproductive System—Hypogonadism is the failure of the testis to develop or properly function. One such syndrome is Klinefelter’s syndrome. It is associated with an XXY chromosomal pattern. These individuals are tall, sterile, and often have breast enlargement. Another example of hypogonadism is Kallman’s Syndrome. This is due to a defect in the secretion of pituitary gonadotropins. Androgen Insensitivity is a disorder in which there is an insensitivity of the target organs to androgens. This leads to feminization in males and was once called testicular feminization.
In contrast to stereotypical depictions of Middle Eastern women as passive victims of patriarchal oppression, women in Egypt have organized themselves for over a century to challenge state authority as well as prevailing gender ideologies and oppressive practices shaping their everyday lives. The last phase has witnessed them going online maintaining blogs that defend their causes. This paper
EpiNews Volume 19 #3: October/November, 2009 Public Health: Always working for a safer & healthier community. Unintentional Poisoning Deaths in Snohomish County: Opioids Most Common Cause Unintentional injuries were the third leading cause of death in2007 in Snohomish County. Unintentional poisonings becamethe leading cause of unintentional injury death in 2004surpassing m