Lecture #11: THE GONADS: MALE REPRODUCTIVE ORGANS

MALE REPRODUCTIVE ORGANS

A.    The male reproductive organs are classified as

1.      Essential organs – gonads of the male; testes

2.      Accessory organ of reproduction:

a.      Genital ducts convey sperm to outside of the body; pair of epididymis, paired vas deferentia, pair of ejaculatory ducts and urethra.

b.      Accessory glands produce secretions that nourish, transport and mature sperm; pair of seminal vesicles, the prostate and pair of bulbourethral glands

B.     The perineum in males is roughly diamond–shaped area between thighs; extends anteriorly from symphysis pubis to coccyx posteriorly; lateral boundary is the ischial tuberosity on either side; divided into the urogenital triangle and the anal triangle.

The Testes

A.    Structures and location

1.      Several lobules composed of seminiferous tubules and interstitial cells of Leydig, separated by septa, encased in fibrous capsule called tunica albuginea.

2.      Seminiferous tubules in testis open into a plexus called rete testis, which is drained by a series of efferent ductules that emerge from the top of the organ and enter the head of epididymis.

3.      Located in scrotum, one testis in each of two scrotal compartments.

B.     Functions

1.      Spermatogenesis – formation of mature male gametes (spermatozoa) by seminiferous tubules.

2.      Secretion of hormone (testosterone) by interstitial cells.

C.    Structure of spermatozoa – consists of a head (covered by acrosome), neck, midpiece and tail; tail is divided into a principal piece and a short end–piece.

Reproductive (Genital) ducts

A.    Epididymis

1.      Structure and location

a.      Single tightly coiled tube enclosed in fibrous casting

b.      Lies along top and side of each testes

c.       Anatomical divisions include head, body and tail

2.      Function

a.      Duct for seminal fluid

b.      Also secretes part of seminal fluid

c.       Sperm becomes capable of motility while they are passing through the epididymis

B.     Vas deferens (ductus deferens)

1.      Structure and location

a.      Tube, extension of epididymis

b.      Extends through inguinal canal, into abdominal cavity, over top and down posterior surface of bladder.

c.       Enlarged terminal portion called ampulla – joins duct of seminal vesicle.

2.      Function 

a.      One of excretory ducts for seminal fluid

b.      Connects epididymis with ejaculatory duct

C.    Ejaculatory duct

1.      Formed by union of vas deferens with duct from seminal vesicle

2.      Passes through prostate gland, terminating in urethra

******  ACCESSORY REPRODUCTIVE GLANDS  ******

A.    Seminal vesicles

1.      Structure and location – convoluted pouches on posterior surface of bladder.

2.      Function – secrete the viscous nutrient–rich part of seminal fluid (60%)

B.     Prostate gland

1.      Structure and location

a.      Doughnut–shaped

b.      Encircles urethra just below bladder

2.      Function – adds alkaline secretion to seminal fluid (30%)

C.    Bulbourethral gland

1.      Structure and location

a.      Small, pea–shaped structures with 1–inch long ducts leading into urethra

b.      Lie below prostate gland

2.      Function – secrete alkaline fluid that is part of the semen (5%)

Supporting structures

A.    Scrotum

1.      Skin covered pouch suspended from perineal region

2.      Divided into two compartments

3.      Contains testis, epididymis and lower part of spematic cord.

4.      Dartos and cremaster muscles elevate the scrotal pouch.

B.     Penis

1.      Structure – composed of three cylindrical masses of erectile tissue, one of which contains urethra.

2.      Function – penis contains urethra, the terminal duct for both urinary and reproductive tracts; during sexual intercourse, penis becomes erect, serving as penetrating copulatory organ during sexual intercourse.

C.    Spermatic cord (internal)

1.      Fibrous cylinders located in inguinal canals.

2.      Enclose seminal ducts, blood vessels, lymphatics and nerves

Regulation of secretion of testicular hormones

1.      Long–loop feedback control system

a.      The hypothalamus secretes gonadotropin–releasing hormone (Gn–RH).

b.      After reaching the pituitary via the hypophyseal portal system, the Gn– RH attaches to receptors on the gonadotropes in the anterior pituitary.

c.       Adenylate cyclase is stimulated, causing the formation of cAMP, which promotes the entry of calcium into the cells. By this process, the secretion of the glycoproteins luteinizing hormone (LH), previously known as interstitial cell–stimulating hormone (ICSH) and FSH is enhanced.

d.     Pituitary secretion of LH stimulates the Leydig cells of the testis to produce testosterone and estradiol. Membranes of these cells contain specific protein receptors for LH. The binding of LH to the receptor causes an increase in cAMP and protein kinase activity.

e.      The metabolic sequence results in an increase in the synthesis of prenenolone and then testosterone, the principal androgen of the testis, and also small amount of estradiol. Some of the testosterone produced is delivered to the seminiferous tubules, where it acts on Sertoli cells to stimulate spermatogenesis and some enters the blood stream.

f.        Testosterone or its metabolite inhibit the release of Gn–RH from the hypothalamus and inhibit the actions of Gn–RH at the anterior pituitary level. These sites have high affinity receptors for testosterone and its metabolites, but testosterone seems to be much more important than estradiol in providing the negative feedback regulation.

g.      FSH activates adenylate cyclase in the Sertoli cells, which consequently causes the aromatization of testosterone to estradiol. Sertoli cells cannot synthesize testosterone from cholesterol since they do not possess the necessary enzymes.

h.      The testosterone found in the cells is the result of diffusion from the interstitial cells of Leydig.

i.        FSH appears necessary only for the initial wave of spermatogenesis that occurs during puberty and is not necessary in the maintenance of spermatogenesis. The negative feedback mechanism of FSH appears to be by inhibin.

j.        Inhibin is a peptide that is synthesized within the Sertoli cells, which can inhibit the release of FSH at the pituitary level as well as at the hypothalamus level to limit Gn–RH secretion.

2.      Short–loop feedback control system

a.      The Leydig cell provides adrenocorticotropic hormone / melanocyte– stimulating hormone (ACTH / MSH) peptides, which stimulate Sertoli cell function.

b.      Beta–endorphin, also produced in the Leydig cells, has inhibitory action in the Sertoli cell.

c.       On the other hand, inhibin, which is produced by the Sertoli cell, stimulates the Legdig cell production of the androgens and the estrogen that diffuses from the Sertoli cells into the adjacent Leydig cells may have the ability to reduce testosterone biosynthesis.

The Testicular Hormone

1.      Androgens

a.      Biosynthesis and metabolism

The androgens are steroid hormones in the C–19 group. The Leydig cells or interstitial cells of the testis are responsible for the production of most androgens in male. There are two major routes for the conversion of pregnenolone to testosterone.

(1)   The first route involves the production of 17–hydroxypregnenolone from pregnenolone. After that conversion, 17–hydroxypregnenolone is converted to dehydroepiandrosterone (DHEA) which goes to androstenediol  and finally testosterone.

(2)   The second pathway involves the production of progesterone, its conversion to 17–hydroxyprogesterone, androstenedione and then testosterone. This pathway is referred to as 4–ene pathway, referring to the double bond between carbons 4 and 5. The enzymes for both of these pathways are located in the smooth endoplasmic reticulum of the cell.

2.      Testosterone

Testosterone is not stored in the testis. Once it is synthesized, it is secreted into the blood, where 97% circulates bound to plasma proteins. These plasma proteins are albumin, transcortin and testosterone binding globulin (TeBG). TeBG has a relatively high affinity for androgens, and approximately 56% of the total bound testosterone is carried by TeBG. The small amount of the free hormone (3%) is responsible for the biologic response since only free hormone can enter target cells. The catabolism of androgens, as with most steroid occurs in the liver with subsequent excretion by the kidney. The principal products of testosterone metabolism are:

a.      Androsterone

b.      Etiocholalone

Laboratory evaluation of testicular function

1.      17–hydroxykorticosteroid

2.      Semen analysis

3.      Chorionic Gonadotropin Stimulation test (hCG)

hCG has the same biologic action as LH, so following an injection of hCG, this hormone will bind to the LH receptors on the Leydig cells and stimulates the synthesis and secretion of testicular steroids. Therefore, the Leydig cells may be directly assessed.

4.      Clomiphene Citrate Stimulation Test

Clomiphene citrate is a non–steroid compound with weak estrogenic activity. It binds to estrogen receptors in various tissues, including the hypothalamus. By preventing the more potent estrogen estradiol from occupying these receptors, the hypothalamus in effect “sees” less estradiol.

5.      Gonadotropoin–Releasing Hormone Test

GnRH administered by repeated injections every 60–120 minutes or by a programmable pulsatile infusion pump for 7–14 days, patients with hypothalamic lesions may have their pituitary responsiveness to GnRH restored, whereas patients with pituitary insufficiency do not.

6.      Testicular biopsy

Clinical significance of testicular function

1.      Male infertility

a.      Pre–testicular causes – usually from hypothalamic or pituitary lesions, leading to the decreased production of the gonadotropins.

(1)   Hypothyroidism

(2)   Cushing’s syndrome

(3)   Malnutrition

(4)   Alcoholic cirrhosis

b.     Testicular causes

(1)   Congenital disorders

(a)   Cryptochordism is unilateral or bilateral absence of the testes from the scrotum because of failure of normal testicular descent from the genital ridge through the external inguinal ring.

(b)   Klinefelter’s syndrome – XXY seminiferous tubule dysgenesis

(2)   Acquired disorders

(a)   Germ cell tumor

(b)   Leydig cell tumor

(c)    Varicocele

(d)  Orchitis

c.       Post–testicular causes

(1)   Mechanical impairment of transport due to

(a)   Defect of male reproductive tract

(2)   Functional impairment of sperm transport due to

(a)   Autonomic nervous system impairment

(b)   Bladder neck incompetence

(c)    Production of sperm antibodies

2.      Syndromes of androgen resistance – results from a single gene mutation causing the affected person to be affected resistant to androgen action.

a.      5–alpha–reductase deficiency – deficient conversion of testosterone to dihydrotestosterone. The patient is a genotypic 46, XY male with normal levels of testosterone but demonstrates predominantly female external genitalia. These individuals are raised as girls but at puberty exhibit virilization.

b.      Defective androgen receptor

(1)   Reifenstein syndrome – partial resistance to the action of testosterone and dihydrostestosterone in X linked disorder.

(2)   Infertile male syndrome – normal males with infertility due to azoospermia or severe oligospermia

c.       Receptor–positive resistance was postulated as a defect after a family was found to have testicular feminization due to androgen resistance.

3.      Impotence  implies erectile dysfunction with or without associated disturbances of libido or ejaculatory ability.