7. Lecture 1 - Reproductive Endocrinology in Males (15pages)

8/12/2019 7. Lecture 1 - Reproductive Endocrinology in Males (15pages)

1/15

ENDOCRINOLOGY OFREPRODUCTION IN MALES

G. A. Bourne

Pre-Clinical Sciences Department

Faculty of Medical Sciences

University of the West Indies

GnRH A HYPOTHALAMICHORMONE

Gonadotropin-releasing hormone(GnRH)

Produced by neurons in theArcuatenucleus (ARC) in mediobasalhypothalamus

GnRH NEURONS

These neurons originate outside the CNS olfactory placode

They migrate along the olfactory nerve tothe arcuate nucleus

Kallmanns syndrome hypogonadotropichypogonadism with associated anosmiaor hyposmia


2/15

HYPOTHALAMUS

Neuronal circuits inthe mediobasalhypothalamusregulating GnRHcollectively knownas the:

Tonic Center orPulse Generator

PULSE GENERATOR

GnRH SECRETION

GnRH released inpulses 8-16

pulses/24h

Transported via theportal system to theanterior pituitary

SPECIFICALLY, THE ARCUATE NUCLEUS

SECRETION


3/15

HYPOTHALAMIC -PITUITARY AXIS

GnRH stimulates thesynthesis and episodicsecretion of: LH and FSH

Activins also stimulateFSH synthesis andsecretion autocrineeffects

LH AND FSH AFFECT THETESTIS

TESTES

2 compartments:

Seminiferous tubules site of spermatogenesis,contains germ cells andSertoli cells

Interstitial tissue - thinweb of connective tissue


4/15

INTERSTITIAL TISSUE

Interstitial tissue -Contains bloodvessels, lymphaticvessels, nerves andLeydig cells

Leydig cells endocrine cellssecreting androgens

STEROIDOGENESIS

Cholesterol synthesis from acetate or fromcholesterol esters or LDLs

Steroidogenesis initiated by the Steroidogenicacute regulatory (StAR) protein - transportscholesterol to the inner mitochondrialmembrane - Rate limiting step

Ineffective StAR lipoid congenital adrenalhyperplasia

STEROIDOGENESIS

In humanspregnenolone isconverted totestosterone via 5

pathway

Mast cells and macro ha es


5/15

PERIPHERAL CONVERSIONOF TESTOSTERONE

Testosterone is also a pro-hormone

Testosterone dihydrotestosterone(DHT)

DHT production catalyzed by 5 reductase

PERIPHERAL CONVERSIONOF TESTOSTERONE

In Sertoli cells, Leydig cells, germcells, bone cells and hypothalamicneurons:

Testosterone estradiol

Catalyzed by aromatase

PERIPHERAL CONVERSIONOF STEROIDS

Some peripheral (extra-glandular) cellshave the necessary enzymes to transformone active steroid into another activesteroid


6/15


7/15

BIOLOGICAL ACTIONS OFANDROGENS FETAL

DEVELOPMENT

Intrauterinedifferentiation -

Mesonephric duct(Wolffian) - T

Urogenital sinusgenital swellings andgenital tubercle - DHT

BIOLOGICAL ACTIONS OFANDROGENS

Peri-natalandrogenexposure

Androgensconverted to

estrogens inhypothalamus

BIOLOGICAL ACTIONS OFANDROGENS PUBERTAL

EFFECTS

Stimulates growth and

development ofaccessory sex organsand external genitalia

Growth of testes notaffected by steroids

wrt differentiation of the male re roductive or ans

This is referredas intrauterineandrogenic effwrt differentiati

Period just before birth and just after birthwhere males are exposed to androgens


8/15

BIOLOGICAL ACTIONS OFANDROGENS PUBERTAL

EFFECTS

Pubertal effects:

Growth of sebaceousglands

Facial & pubic hair,recession of temporalhairline

Pubertal growth spurt

Enlarges the larynx &thickens the vocalchords

BIOLOGICAL ACTIONS OFANDROGENS - PUBERTAL

EFFECTS

Initiate spermatogenesis

Initially bothtestosterone & FSHrequired

Can be maintained withhigh levels of T alone


After puberty:

Maintain secondary sex organs

Maintain spermatogenesis

Maintain secondary sex characteristics

Maintain sex drive (libido) and ability to haveerections


9/15


Stimulate the maturation of spermatozoa

Stimulate reabsorption of testicular fluid toconcentrate sperm mediated by E2

Prolong the life span of spermatozoa inthe epididymis


Anabolic steroids -protein synthesis -positive nitrogenbalance

Stimulates growth ofmuscle and bone

Stimulates fusion of

epiphyses of long bones E2


Erythropoietin

Red blood cellproduction

Also stimulate rate ofmaturation oferythroid precursors

Once sperm is stored in the epididymis, they do have a certain life span. In

the absence of testosterone, this life span is significantly decreased

referred to as anabolic steroids


10/15


Regulate the synthesis of hepaticproteins

Decreases the synthesis of transportproteins for the lipid-soluble hormones

Increases VLDL & LDL while decreasesHDL higher risk of coronary arterydisease in men?

SUMMARY OF ESTROGENEFFECTS

Negative feedback effects at the level of thehypothalamus

Epiphyseal fusion

Mediate some male reproductive behaviors

Reabsorption of testicular fluid to concentratesperm

SERTOLI CELLS

Forms the circumferenceof the seminiferous

tubules Interconnected by

junctional complexes

(include gap junctions,tight junctions) blood-testis barrier

2 compartments basaland adluminalcompartments

on the pulse generator

Done in conjunction with the thyroid hormones

Basis of increased libido & maintenance and ability to have erections

aka nerve cells or

sustentacular cells


11/15

BLOOD-TESTES BARRIER

Myoid cells plus junctional complexes ofSertoli cells

Protects germ cell derivatives from:

Harmful chemicals

Activation of autoimmume responses

Provides suitable micro-environment forspermatogenesis

ENDOCRINE FUNCTIONS OFSERTOLI CELLS

FSH activates the enzyme aromatase

Aromatase catalyzes the conversion oftestosterone into estradiol


Estradiol inhibits T production by:

Decreasing LH receptors

Inhibiting 17 hydroxylase and 17desmolase

peritubular cells

Functions of the BTB:

1. To protect the germ cells from harmful chemicals

2. To prevent the activation of autoimmune responsethe BTB is destroyed, as a result of injury or infectiothen the immune system will be activated and soantibodies will then gain access into the seminiferoutubules. The end result will be the destruction of the

cells. These individuals will then become sterile. Thewill be inflammation of the testes known as autoimmorchitis resulting in infertility)

3. Provide a suitable micro-environment forspermatogenesis. For example, there is increasedpotassium secretion into the lumen of the seminiferotubules which will inhibit sperm motility. Therefore duthe transportation from the testes to the epididymis,sperm motility will be inhibited.


12/15

OTHER HORMONES AFFECTINGTESTOSTERONE PRODUCTION

PRL enhances LH-stimulated testosteroneproduction

Gonadocrinin (testicular GnRH) inhibits LH-induced testosterone production

Activin also inhibits LH-stimulatedtestosterone production

Inhibin neutralizes activin effects


FSH stimulates the secretion of Inhibins:

Family of heterodimeric glyco-proteinscontaining and chains

2 subunits -a and b Inhibin A a and

inhibin B b Inhibin B secreted in males

ACTIVINS

Also a dimer the 2 subunits of inhibin

3 isoforms of activin:

Activin A aaActivin B b bActivin AB -a b

NHIBINS are:

2 isoforms of the beta chains which results in 2 t es of inhibins:

somer of inhibin

ally secreted in

s:

HOMODIMER

HOMODIMER


13/15

ACTIVINS

Activins produced by:

Gonadotropes

Sertoli cells

Leydig cells

Germ cells and derivatives

Peritubular cells

Exert paracrine/autocrine effects

ACTIONS OF ACTIVINS

Pituitary - autocrine effects to FSHsynthesis and secretion

Immature testes stimulate germ cellproliferation, while inhibiting Sertoli cellfunctions.

Later stages stimulate Sertoli cellproliferation, while inhibiting proliferationof spermatogonia A.

Leydig cells - inhibits testosteroneproduction

FOLLISTATIN (FS)

Glycoproteins produced in cells thatproduce activins

Follistatins bind activins - prevents themfrom binding to their receptors

Effectively exert antagonistic actions toactivins, since they limit the exposure ofactivins to target tissues

ct v ns w most y exert autocr ne e ects


14/15

ACTIONS OF INHIBINS

Inhibit the effects of activins

Inhibit spermatogonial proliferation

Prevents activin-induced inhibition oftestosterone production

ACTION OF INHIBINS

Inhibit FSH secretion inresponse to activin only

Does not affect GnRH-induced gonadotropinsecretion

OTHER ACTIONS OF FSH

Secretion of androgen binding protein (ABP)

Reservoir to maintain high concentrations inseminiferous tubules

Released into lumen of seminiferous tubules high concentrations to the epididymis

Transferrin and ceruloplasmin

from sertoli cellsStimulate the

P serves as a of testosterone in the

which is necessary for continued spermatogenesis


15/15

ACTIONS OF FSH

Secretion ofplasminogen activator

Converts plasminogento plasmin

Plasmin (and otherproteases) regulatemigration of germ cellsfrom basal to adluminalcompartments

7. Lecture 1 - Reproductive Endocrinology in Males (15pages)

Documents

Transcript of 7. Lecture 1 - Reproductive Endocrinology in Males (15pages)