Block 2: IQ Group 12: Learning Objective Wiki

Case #3

1. List hypothalamic, pituitary, gonad axis involved in male sexual development.

The hormones involved in male sexual development are:

Gonadotropin Releasing Hormone (GnRH) from the hypothalamus,

Luteinizing Hormone (LH) from the anterior pituitary/adenohypophysis,

Follicle-Stimulating Hormone (FSH) from the anterior pituitary,

Testosterone from the Leydig cells,

Dihydrotestosterone (DHT, a testosterone metabolite) from prostate gland, adrenal glands, testes and hair follicles,

Estrogen (mainly Estradiol) from aromatization of testosterone, and to a very small extent, the testes,

Activin (FSH stimulant) from testes and anterior pituitary gland, and

Inhibin (FSH and GnRH inhibitor) from the Sertoli cells - Paul

2. Demonstrate knowledge of the hypothalamic, pituitary, gonad axis, its feedback, and regulation by drawing a detailed diagram of this system.

This diagram is copyrighted, so I'm going to post a document on googlegroups called Case3Diagram- Alex

3. Describe the similarities in the neuroendocrine control of male and female reproduction.

In both males and females, gonadal function is driven by the hypothalamic-pituitary axis. At puberty, the hypothalamus (arcuate nuclei) begins to secret GnRH in a pulsatile pattern, which drives a parallel pulsatile secretion of FSH and LH from the anterior pituitary. In turn, this pulsatile activity causes the testes and ovaries to secrete their respective sex hormones. A helpful way to think of it is that everything above the diaphragm is the same, and everything below differs by gender. - Mandy

6. Describe the anatomy of the testes.

The volume of an average testis is approximately 20 mL. The functions of the testicles are androgen and sperm production. The Leydig cells in the testis produce testosterone, while the Sertoli cells support the maturation of spermatogenic cells into sperm. The Sertoli cells are also responsible for establishing a blood–testis barrier.

The epididymis is located on the posterolateral aspect of the testis. Spermatogenesis occurs in the seminiferous tubules of the testes, and mature sperm are conducted by the efferent ducts into the epididymis where they are stored. Under sympathetic stimulation, sperm are conducted along the vas deferens in a process termed emission. The vas deferens is joined by the seminal vesicle to form the ejaculatory duct. The semen that is deposited into the urethra is carried along the urethra under somatic enervation during ejaculation. - Andrea

7. Describe how testosterone is produced and list the target tissues for testosterone action in the male.

Most of the testosterone (around 95%) in the male body is synthesized and secreted in the Leydig cells of the testes. Leydig cells convert cholesterol (either synthesized de novo or taken up from LDLipoproteins) to testosterone via five enzymes in the mitochondria. Other organs such as the adrenal glands also produce androgens in men and women.

Most of the secreted testosterone binds to the proteins: sex hormone-binding globulin (SHBG), albumin and corticosteroid-binding globulin. Free testosterone diffuses into the cell and either binds to its androgen receptor in the nucleus or is converted to dihydrotestosterone (DHT), which also binds a nuclear receptor. These receptors are transcription factors that lead to the synthesis of proteins involved in growth and development. In some tissues like the brain, testosterone is converted to estradiol in order to affect transcription.

Testosterone is needed for development of male internal and external genitalia in the fetus and during puberty. Spermatogenesis requires high concentrations of testosterone, which is localized in the seminiferous tubules by the SHBG secreted by the Sertoli cells. Testosterone also stimulates growth of skeletal muscle, the larynx, the epiphysial plates, pubic, axillary and male sexual hair. --Dan

Case #4

1. List the hypothalamic, pituitary, thyroid and ovarian hormones involved in menstruation and lactation.

The hormones involved in menstruation and lactation are:

Gonadotropin Releasing Hormone (GnRH) from the hypothalamus,

Luteinizing Hormone (LH) from the anterior pituitary/adenohypophysis,

Follicle-Stimulating Hormone (FSH) from the anterior pituitary,

Prolactin (aka Luteotropic Hormone, LTH) from the adenohypophysis,

Estrogen (mainly Estradiol) from granulosa cells, adrenal cortex and aromatase action on testosterone,

Progesterone from the ovaries and adrenal cortex,

Activin (FSH stimulant) from ovaries, adenohypophysis, and

Inhibin (FSH and GnRH inhibitor) from the granulosa cells - Paul

2. Demonstrate knowledge of the hypothalamic, pituitary, ovarian axis, its feedback, and regulation by drawing a detailed diagram of this system.

This diagram is copyrighted, so I'm going to post a document on googlegroups called Case4Diagram- Alex

3. Identify the hormonal interactions that stimulate the ovary to synthesize estrogen.

The ovaries are made up of three cell types, germ cells, granulosa cells and theca cells. The ovarian steroid hormones, progesterone and estrogen, are synthesized by the ovarian follicles through the combined functions of granulosa and theca cells. Theca cells synthesize and secrete progesterone, which is stimulated by LH. Theca cells also synthesize testosterone, and testosterone diffuses from the theca cells to the nearby granulosa cells, which contain aromatase. Aromatase converts testosterone to 17β-estradiol (the major ovarian estrogen) in the granulosa cells. This step in the biosynthetic pathway is stimulated by FSH. (Granulosa cells are the only ovarian cells with FSH receptors.) -Mandy

6. Describe the typical symptoms and signs of hypothyroidism.

Common symptoms of hypothyroidism include weight gain, fatigue, lethargy, depression, weakness, dyspnea on exertion, arthralgias or myalgias, muscle cramps, paresthesias, cold intolerance, constipation, dry skin, headache, carpal tunnel syndrome, and menorrhagia. Physical findings can include bradycardia, diastolic hypertension, thin, brittle nails, thinning of hair, peripheral edema, puffy face and eyelids, and skin pallor or yellowing. Delayed relaxation of deep tendon reflexes may be present. Patients may have a palpably enlarged thyroid (goiter) that arises due to elevated serum TSH levels or the underlying thyroid pathology, such as Hashimoto thyroiditis.

Less common symptoms of hypothyroidism include diminished appetite and weight loss, hoarseness, decreased sense of taste and smell, diminished auditory acuity, and dysphagia or neck discomfort. Although most menstruating women have menorrhagia, some women have scant menses or amenorrhea. Physical findings may include thinning of the outer halves of the eyebrows; thickening of the tongue; hard pitting edema; and effusions into the pleural and peritoneal cavities as well as into joints. Galactorrhea may also be present. - Andrea

7. Describe the laboratory tests used to diagnose hypothyroidism.

The most important test for hypothyroidism is serum level TSH. Additionally measurement of free throxine (T4) or free triiodothyronine (T3) is helpful. TSH is evelated and T4 absent in hypothyroidism. Testing for thyroid autoantibodies (antiperoxidase, antithyroglobulin) is indicative of Hashimoto thyroiditis, a common cause of hypothyroidism. --Dan