Sex Hormones - Male Reproductive Function - Flashcards in University Pharmacy

What are the two main physiological functions of the testes?

Production and release of testosterone. Spermatogenesis (production of mature gametes/sperm cells) - Both controlled by hypothalamic-pituitary-gonadal axis

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Describe features of the HPG axis

System responsible for controlling reproductive function in males and females. Hypothalamus releases GnRH which acts on anterior pituitary. Anterior pituitary releases FSH and LH. Stimulates release of testosterone from testis in males.

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Where is the hypothalamus located?

Located at the base of the brain near the pituitary gland (pre-optic area)

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Describe features of the GnRH neurons (1)

Cell bodies in pre-optic area of hypothalamus extend to median eminence and release GnRH into pituitary portal blood system. GnRH is released in regular pulses. GnRH not detected in the blood (not released in wider circulation)

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Describe features of the GnRH neurons (2)

LH/FSH released from gonadotroph cells in the anterior pituitary in response to GnRH. LH/FSH also released as regular pulses

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Describe features of the GnRH neurons (3)

LH and FSH are released together into circulation from anterior pituitary in response to GnRH

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What are the effects of LH and FSH on the male reproductive system?

LH stimulates production of testosterone in the testes. FSH stimulates growth and maturation of testes and spermatogenesis

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What is the effect of testosterone on the hypothalamus and anterior pituitary gland?

Testosterone goes into wider circulation and has a negative feedback effect at the level of the hypothalamus and at the level of the anterior pituitary gland

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Describe the anatomy of the male genitalia (1)

Testes located outside the main body cavity (act effectively at a temperature slightly below body temperature). Densely packed network of tubing, epididymis. Two main compartments. Tubular structures (seminiferous tubules)

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Describe the anatomy of the male genitalia (2)

And cells outside tubules e.g. blood vessel supply (Leydig cells)

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Describe features of Leydig cells (1)

Cells in testes responsible for production/release of testosterone, located outside seminiferous tubules, stimulated by LH (released from anterior pituitary), LH receptors

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Describe features of Leydig cells (2)

LH stimulates the synthesis and release of testosterone and other androgens from Leydig cells. LH stimulates cholesterol desmolase (steroid hormone synthesis)

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Describe features of Leydig cells (3)

Conversion of cholesterol to pregnenolone (converted to testosterone, released into circulation)

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What is the main precursor for testosterone?

Pregnenolone

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What is the correlation between the amount of testosterone and testis volume?

Amount of testosterone directly proportional to size/volume of testes. Increased testosterone released from growing testes drives formation of secondary sexual characteristics e.g. facial hair, voice breaking

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What are the effects of testosterone?

Male hormone - anabolic, primary and secondary sexual characteristics, libido and sexual behaviour, stimulates spermatogensis

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Describe features of the seminiferous tubules

Where spermatogenesis takes place, production/release of mature of sperm cells. Two main cell types - Sertoli cells (larger cells, span from basal laminar tubule to lumen in the centre), spermatogonial stem cells (smaller cells)

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What is the function of spermatogonial stem cells?

Responsible for sperm production (replicate to form sperm cells)

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What are the functions of Sertoli cells?

Support physical structures of seminiferous tubules, provide nutrition, protection, regulation of process

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State features of spermatogenesis

Starts at puberty. Maintains species. Mitosis followed by meiosis. 120 million sperm/day or 1500/s

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What is spermatocytogenesis?

Spermatogonial stem cells (diploid - 46 chromosomes) divide by mitosis to replace themselves and produce spermatocytes (cells which become sperm)

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What are the three sub types of spermatogonial stem cells? (1)

Type A (d), d for dark appearance, replicate by mitosis to provide a constant supply of type A(d) and type A(p) cells (p for pale appearance). Type A(p) - divide by mitosis to produce type B cells

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What are the three sub types of spermatogonial stem cells? (2)

Type B cells divide by mitosis to primary spermatocytes

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What is spermatidogenesis? (1)

Primary spermatocytes produce spermatids through meiosis. Second phase. Cells start to move towards lumen of seminiferous tubules. Primary spermatocyte (46 chromosomes, diploids)

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What is spermatidogenesis? (2)

Meiotic division to form secondary spermatocytes (23 chromosomes, haploid). Second meiotic division to form spermatids (23 chromosomes, 1 copy of each chromosome, contains genetic material)

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What is spermiogenesis? (1)

Final process, spermatids (lack of structure), process of generating characteristics of a sperm structure. 4-phase process to convert symmetrical spermatids into mature sperm

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What is spermiogenesis? (2)

Spermatid attached to Sertoli cell. Golgi phase - golgi apparatus creates a vesicle of enzymes around nucleus (golgi faces Sertoli cell). Mitochondria start to move to other side of cell. Centriole forms axoneme, cytoskeleton core of tail

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What is spermiogenesis? (3)

Cap phase - spermatid DNA condensed in nucleus. Golgi apparatus surrounds nucleus and enzyme vesicle forming acrosomal cap. Acrosome phase - axoneme extends to become tail of sperm, temporary cytoskeleton structures (manchettes) support growing tail

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What is spermiogenesis? (4)

Attach nucleus to cytoskeleton tail. Maturation phase - excess cytoplasm phagocytosed by Sertoli cells to produce mature sperm. Left with head of sperm containing nucleus and acrosome, mitochondria in middle piece, tail extending outwards

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Describe features of mature sperm

Though mature, sperm in the seminiferous tubules are not motile. Non-motile sperm are transported to the epididymus where they are stored and gain motility

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Sertoli cells are regulated by which hormone?

FSH - essential for spermatogenesis regulation

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What are the multiple functions of Sertoli cells? (1)

Form the blood-testis barrier. Release androgen-binding protein. Release inhibin for feedback on the pituitary. Secrete supporting fluid into lumen. Phagocytose residual cytoplasm from spermiogenesis.

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What are the multiple functions of Sertoli cells? (2)

Release of a range of other proteins such as GDNF and anti-mullerian hormone

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Describe features of the blood-testis barrier (1)

Barrier between blood and seminiferous tubules (tight junctions). Allows Sertoli cells to control environment within the lumen. Protects developing sperm from any toxins (prevent mutations of sperm)

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Describe features of the blood-testis barrier (2)

Separates developing sperm from the immune system which would otherwise mount an autoimmune response. Sperm not recognised as self-cells (would be targeted by the immune system/destroyed)

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Describe features of the androgen-binding protein (1)

Spermatogenesis requires high levels of testosterone around the developing sperm. ABP binds to testosterone in the lumen, making testosterone less lipophilic. Concentrates testosterone in the lumen, increasing fertility

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Describe features of the androgen-binding protein (2)

ABP prevents testosterone leaving/passing through blood-testis barrier. Testosterone can pass from Leydig cells and pass through blood-testis barrier. Seminiferous tubules need high levels of testosterone

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Testosterone is under the control of which hormone?

LH (FSH can't have negative feedback through testosterone)

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Describe the roles of the hormones in the HPG axis (1)

LH stimulates interstitial Leydig cells to produce testosterone (negative feedback to hypothalamus and pituitary). Some testosterone remains in the testes. FSH stimulates Sertoli cells to produce ABP and inhibin

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Describe the roles of the hormones in the HPG axis (2)

ABP binds to testosterone to stimulate spermatogenesis (high concentrations of testosterone in seminiferous tubules, formation of mature sperm). Testosterone also feeds back to suppress LH secretion (testosterone can be converted to other androgens)

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Describe the roles of the hormones in the HPG axis (3)

Inhibin produced by Sertoli cells feeds back to suppress FSH secretion

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What is the role of prolactin?

Released from the pituitary, can affect male fertility. Increases LH receptor expression on Leydig cells resulting in increased testosterone release and increased spermatogenesis

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Describe features of sperm transport (1)

*********** (deposition of sperm in vagina, acidic). Cervix (mucous barrier and crypts as sperm reservoirs, sperm motility is important). Uterus and fallopian tubes (mild contraction to propel sperm towards egg)

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Describe features of sperm transport (2)

Fertilisation occurs in ampullary region of the tube

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Describe features of sperm capacitation (1)

Takes place in the uterus. Cholesterol/glycoproteins removed from sperm cell surface by enzymes (e.g. heparin) in the uterus. Switching on of sperm through increased Ca influx

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Describe features of sperm capacitation (2)

Hyperactivity of sperm (increased motility, sperm gets to fallopian tube for fertilisation)

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What is the acrosome reaction? (1)

Triggered by sperm cell being in contact with oocyte. Interaction with ZP3 protein on oocyte membrane (match between oocyte and sperm cells), prevents cross-species fertilisation

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What is the acrosome reaction? (2)

Acrosome releases hyaluronidase/acrosin enzymes to break through egg coating allowing fertilisation

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What is oocyte activation?

Following fertilisation, cortical granules are released and the oocyte membrane becomes impermeabl to other sperm. Formation of male and female pronuclei

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Give an example of disturbances in testes function at a genetic level (1)

Klinefelter syndrome - male with XY chromosomes also has an additional X chromosome (has 47 chromosomes instead of 46). Effects vary in individuals, may not have symptoms but can result in hypogonadism, female characteristics and reduced fertility

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Give an example of disturbances in testes function at a genetic level (2)

Affects between 1:500 and 1:1000 males (common). Not diagnosed unless there is genetic screening

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Give an example of disturbances in testes function at the hypothalamic level (1)

Kallman syndrome - GnRH neurones normally originate from olfactor region of the brain and migrate to hypothalamus. Genetic mutations affect olfactory bulk and stop GnRH neurones developing. Leads to lack of GnRH neurones, no reproductive function.

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Give an example of disturbances in testes function at the hypothalamic level (2)

Causes a loss of sense of smell. Affects around 1:10,000 males (rare)

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Give an example of disturbances in testes function at the pituitary level (1)

Hyperprolactinaemia - abnormally high levels of circulating prolactin which inhibits GnRH. Can be caused by pituitary tumours. Also side effect of prescription drugs affecting dopamine (D2 antagonists, reduced dopamine, high levels of prolactin)

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Give an example of disturbances in testes function at the pituitary level (2)

Male symptoms include decreased libido and reduced fertility

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Give an example of disturbances in testes function at the target tissue level (1)

Androgen insensitivity syndrome - genetic defects in androgen receptors reduce sensitivity to testosterone and other androgens. Extend of androgen insensitivity can vary resulting in wide range of severity

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Give an example of disturbances in testes function at the target tissue level (2)

Mild effects but complete androgen insensitivity can result in female body development despite XY chromosomes

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Which factors affect sperm production? (1)

Hormones (increase in testosterone, increase in sperm concentration, use of male contraception decreases testosterone levels which decreases sperm concentration). Use of steroids will suppress HPG axis/reduce fertility

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Which factors affect sperm production? (2)

Non-hormonal factors (environment, climate/heat, radiation, air pollution, food chain pollution, stress, increase in oxidative stress). Male contraceptive - difficult to reduce sperm count completely

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Which factors affect sperm production? (3)

E.g. non-hormonal factors/environment (presence of high oestrogen levels e.g. women using contraceptive patches)

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Summarise features of male reproductive function (1)

Testicular function depends on delicate interaction between 2 testicular components. Control mainly via HPG axis. Disturbance of testicular function can occur at genetic, hypothalamic, pituitary or end-organ level

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Summarise features of male reproductive function (2)

Environmental factors could also affect testicular function

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Sex Hormones - Male Reproductive Function

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