Hormonal Control of Reproduction in - PowerPoint Presentation

Slide1

Hormonal Control of Reproduction in the Male

SpermatogenesisSpermatogenesis goes on continuously from puberty to senescence along the entire length of the seminiferous tubulesThough a continuous process, spermatogenesis can be divided into three discrete phases: Mitotic divisions, which maintain a stem cell population of

spermatogonia

and provide the cells destined to become mature sperm

Meiotic divisions, which reduce the chromosome number and produce a cluster of haploid spermatids

Transformation of spermatids into mature spermatozoa, a process involving the loss of most of the cytoplasm and the development of flagella

Control of Testicular Function Physiological activity of the testis is governed by two pituitary gonadotropic hormones

follicle

stimulating hormone

(

FSH)

and luteinizing hormone (LH)The same gonadotropic hormones are produced in pituitary glands of men and womenFSH and LH are closely related glycoprotein hormones that consist of a common α subunit and unique β subunits that confer FSH or LH specificity

Both gonadotropins are synthesized and secreted by a single class of pituitary cells, the gonadotropesTheir sites of stimulation of testicular function

, however, are discrete:

LH

acts on the

Leydig

cells and FSH acts on the Sertoli cells in the germinal epitheliumControl of Testicular Function

Control of Testicular FunctionLeydig Cells

The principal role of

Leydig

cells is synthesis and secretion of testosterone in response to stimulation by

LH

In addition to stimulating steroidogenesis, LH controls: the availability of its own receptors (downregulation)and governs growth and differentiation of Leydig cells

In male embryos androgen secretion by the

Leydig

cells is initiated by human chorionic gonadotropin (

hCG

)

Control of Testicular FunctionLeydig Cells

As with the

adrenal cortex,

the initial step in the synthesis of testosterone is the conversion of cholesterol to

pregnenolone

In maintaining the functional integrity of the Leydig cells, LH maintains the levels of all steroid transforming enzymesTestosterone released from Leydig cells may diffuse into:

nearby

capillaries for transport in the general

circulation

or

it may diffuse into nearby seminiferous tubules

where

it performs its essential role in

spermatogenesis

Control of Testicular FunctionLeydig Cells

The testes also secrete small amounts of estradiol and some

androstenedione

, which serves as a precursor for

extratesticular

synthesis of estrogens

Leydig

cells are the

main source

of testicular

estrogens

Control of Testicular FunctionLeydig Cells Estradiol is present in seminal fluid and is essential for fluid

reabsorption

in the rete

testis

The

presence of estrogen receptors in the epididymis and several testicular cells, including Leydig cells, suggests that estradiol may have other important actions in normal sperm formation and maturation

Control of Testicular FunctionGerminal Epithelium The function of the germinal epithelium is to produce large

numbers

of sperm that are capable of

fertilization

The

Sertoli cells harbor and nurture sperm as they matureSertoli cells are the only cells known to express FSH receptors in human males and therefore are the only targets of FSHFSH increases Sertoli cell proliferation and differentiation

in the immature testis and maintains the

functional

state of the stable population of

Sertoli

cells in

the

mature

testis

In

its absence testicular size is severely

reduced

and sperm production, which is limited by

Sertoli

cell

availability, is severely restricted

Sertoli cells lack receptors for LH but are richly endowed with androgen receptors, indicating that the actions of LH on Sertoli cell function are indirect, and are mediated by testosterone

FSH and testosterone have overlapping actions on

Sertoli

cells and act

synergisticallyTestosterone is indispensable for spermatogenesis FSH is required for production of normal quantity and quality of spermControl of Testicular Function

Germinal Epithelium

Testosterone: Secretion and Metabolism Testosterone is the principal androgen secreted by the mature testisNormal

young men produce about 7

mg

each

day

, of which less than 5% is derived from adrenal secretionsTestosterone in blood is largely bound to plasma protein, with only about 2 to 3% present as free hormoneAbout half is bound to albumin, and slightly less to sex hormone-binding globulin (SHBG), which is also called testosterone-estradiol-binding globulin (

TeBG

)

Testosterone: Mechanism of ActionLike other steroid hormones, testosterone penetrates the target

cells

whose growth and function it

stimulates

Androgen

target cells generally convert testosterone to 5 α-dihydrotestosterone before it binds to the androgen receptorThe androgen receptor is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily

Testosterone (T)

Androgen receptor (AR)

5 α-

dihydrotestosterone

(DHT)

The thickness of the arrows reflects the quantitative importance of each reaction

Testosterone:Effects on the Male Genital Tract

Testosterone promotes growth, differentiation, and function

of

accessory organs of

reproduction

Maintenance of normal reproductive function in the adult also depends on continued testosterone secretionIt also affects organs directly related to transport and delivery of sperm

Testosterone: Effects on secondary sexual characteristicsContributes to the morphological and psychological components of

masculinity

Stimulate

growth of

pubic,

chest, axillary, and facial hair Adequate amounts of Dihydrotestosterone allow expression of genes for baldnessGrowth and secretion of sebaceous glands in the skin are also stimulated, a phenomenon undoubtedly related to the acne of adolescence

Stimulates growth of the larynx and thickening of the vocal chordsAdolescent growth spurt results from the interplay of testosterone and growth hormonePromote growth of muscleTestosterone also stimulates red blood cell productionIn both men and women androgens increase sexual drive ( libido )

Testosterone:

Effects

on secondary sexual characteristics

Sexual DifferentiationThe early embryo

has

the potential to form either testes or ovaries and develop

either

the male or female

phenotypeDifferentiation of the testes depends upon the transient expression of a single gene on the Y chromosome (SRY, sex-determining region of the Y chromosome)It encodes a transcription factor that stimulates expression of some genes and repress expression of

others

SOX 9: transcription factors

FGF9:

autocrine factor

(fibroblast growth factor 9)

DHH: desert hedgehog

PDGF: platelet-derived growth factor

AMH:

antimüllerian

hormone

Development of internal reproductive ducts and their derivativesWolffian

ducts

are progenitors of the upper male genital tract

The

müllerian ducts are the progenitors of the upper female genital tract Thus, regardless of its genetic sex, the embryo has the potential to develop supposedly either as male or female

The

Sertoli

cells begin to secrete the

antimüllerian

hormone (AMH), which,

causes

epithelial

cells

of the

müllerian

ducts to undergo

apoptosis

A similar fate awaits the

wolffian

ducts unless they are rescued by testosterone produced by the developing

Leydig

cells

Regulation of Testicular Function Testicular

function depends

on stimulation

by

two pituitary hormones, FSH and

LHWithout them, the testes lose spermatogenic and steroidogenic capacitiesSecretion of these hormones by the pituitary gland is driven by the central nervous system through its secretion of the

gonadotropin releasing

hormone (

GnRH

)

Signals

from the testis are

inhibitory

Castration results in a prompt increase in secretion of both

FSH

and

LH

FSH stimulates the

Sertoli

cells to synthesize and secrete a glycoprotein called

inhibin

, which acts as a feedback inhibitor of FSH