Académique Documents
Professionnel Documents
Culture Documents
physiology
By
Khorrami Ph.D.
khorrami4@yahoo.com
http://khorrami1962.spaces.live.com
Testis
• Seminiferous tubules
– 900*50cm …..450m
– 80% volume of testis
• Rete testis(anastomosing tubule)
• Efferent ductules
• Epididymis
– 5m long
– Head …immature sperm
– Body….sperm maturation
– Tail ….sperm maturation
• Vas deferens …. Decapacitation
• Ejaculatory duct
Spermatogenesis needs
• Sertoli
• Leydig
• Germ cells
• Myoepithelial cells
• Epithelial cells
Spermatogenesis
• Mitosis
• Miosis
• Spermiogenesis
• spermiation
Spermatogenesis
SPERMATOGONIA (DIPLOID)
MITOSIS
PRIMARY
SPERMATOCYTES
(DIPLOID)
12
SPERMATOGENESIS
PRIMARY SPERMATOCYTES
MEIOSIS I
SECONDARY SPERMATOCYTES
(HAPLOID)
MEIOSIS II
SPERMATIDS (HAPLOID)
SPERMIOGENESIS
SPERMATOZOA (HAPLOID)
13
FROM SPERMATID TO SPERM
15
16
SERTOLI CELL17
Spermatogenesis
• Inhibited by:
• Toxiphole
• Hypokalemia
Functions of Sertoli cells
• Blood-testis barrier(sertoli-cell barrier) by
tight junction
– Adluminal compartment
– Basal compartment
• Supportive effects on germ cells
• Nutritive effects on germ cells
• Secretions
FUNCTIONS OF SERTOLI CELLS
• Secrete ANDROGEN BINDING PROTEIN &
LUMINAL FLUID.
• Secrete PARACRINE AGENTS Stimulating
proliferation & differentiation.
23
FUNCTIONS OF SERTOLI CELLS
• Secrete the regulatory protein INHIBIN.
• Secrete paracrine agents: FACILITATING
LEYDIG CELL FUNCTION.
• PHAGOCYTOSIS of defective sperm
• Secrete MULLERIAN INHIBITING
HORMONE(MIH)
24
Secretions of Sertoli cells
• Mullerian inhibitory factor (MIF)
• Aromatase
• Androgen binding protein (ABP)
• Inhibin
• Estrone/estradiol
• DHT
• GnRH-like peptide
• Ceruloplasmin
• Plasminogen activator
• Follistatin
• IGF-1
• TGF
• Transferrin
• Cytokines
Functions of leydig cells
• Steroidogenesis …8-18th week of gest.
• LH receptor/PRL(potentiate LH function)
• Testosteron ..5-7mg/day
• Androstenedione
• Relaxin-like factor
• A good marker for fully differentiated adult-
type Leydig cells
• Weakly expressed in prepubertal
• Immature Leydig cells
– By insulin-like factor 3 gene
Relaxin-like factor 3(RLF)
• In estrogen-induced cryptorchidism, RLF
levels in the testis are significantly reduced
• RLF secreted by theca cells of small antral
follicles
• RLF secreted by the corpus luteum of the
cycle and pregnancy
Testicular steroidogenesis
MALE REPRODUCTION: HORMONAL REGULATION
HYPOTHALAMUS
- ve feedback
GONADOTROPIN RELEASING HORMONE
ANTERIOR PITUITARY
- ve feedback
FSH LH
TESTES
S
E LEYDIG CELL
R
T
O TESTOSTERONE
L
I REP.TRACT
CELL SPERMATOGENESIS
& OTHER ORGANS
INHIBIN 29
SEMEN ANALYSIS
• A test for infertility
• Semen contain:
– Sperms
– Secretions:
• Seminal vesicles
• Prostate
• Cowper’s glands
• Bulbo-urethral glands
30
SEMEN ANALYSIS
• Volume: 2.5 to 3.5 ml/ejaculate
• Sperm count: 100 M/ml.
• <20% abnormal.
• <20 M/ml, sterile
• Sperm speed: 3mm/min.
• Reach fallopian tube 30- 40 min after coitus.
31
SEMEN: COMPOSITION
32
SEMEN
• Liquid when ejaculated
• Coagulates:
– In vitro
– In vagina
• Undergoes secondary liquefaction after
15 min.
33
SPERMATOZOA
• Fertile up to 24 to 48 hrs after deposition.
• Motile, for 48 – 60 hrs.`
34
Semen production
• Seminal vesicle (60%)
• Prostate (30%)
• Bulbouretral gland (cowper)
• Seminiferous tubule
Semen composition
• Fructose (for anaerobic metabolism of sperm )….sem.ves
• Glucose, A.A. and sorbitol (for aerobic metabolism of sperm ) ….sem.ves
• Hormones (androgens, estrogens, progesterone)
• Decapacitation factors (cholesterol/esterol) ….sem.ves
• Prostoglandins ….sem.ves
• Citrate
• Ascorbic acid ….sem.ves
• Lecithin ….sem.ves
• Phosphoryl choline ….sem.ves
• Potassium
• Acid phosphatase
• Phosphate
• HCO3-
• Acrosin inhibitor
• Spermine (odor- coagulation) .....prostate
• Sperm coating proteins.....prostate
• Fibrinolysin .....prostate
• Zinc .....prostate
Testosterone & other steroids in
man
• Testis 95%
• Adrenal 5%
• Total: 5-7mg/day
• DHT 50-100µg/day
• 17α-OH-progesterone 1-2mg/day
• Estradiol 10-15µg/day
Testosterone & other steroids
• Castration →increase in LH & FSH
• Castration+ androgen →increase in FSH only
• Role of inhibin
Androgen in plasma
• SHBG 40%
• Albumin 47%
• Other proteins
Metabolism of androgens
• By urine
• Excreted as 17KS 50%
• Gluco & sulphoconjugation in liver
• ↓
• Urinary 17-KS
– Testis 30%
– Adrenal 70%
FUNCTION OF PENIS IN COITUS
(SEXUAL INTERCOURSE)
• Erection
• Ejaculation
50
ERECTION
• VASCULAR:
– SMALL ARTERIAL DILATATION
– VENOCONSTRICTION
• PARASYMPATHETIC FACILITATION
• SYMPATHETIC INHIBITION
– SMOOTH MUSCLES RELAX
51
PENILE ERECTION: REFLEX PATHWAYS
INPUT FROM
THOUGHTS MECHANORECEPTORS
EMOTIONS OF PENIS
SIGHT, SMELL
NEURONS TO PENIS
NEURONS RELEASE nonCholinergic
NEUROTRANSMITTER (NO)
PENIS
ARTERIAL DILATATION + VENOCOMPRESSION
= ERECTION
52
EJACULATION
• Sympathetic facilitation
• Skeletal muscles contract
• Two events:
1. EMISSION: Smooth muscles contract &
semen sent into urethra
2. EXPULSION: Rapid contraction of
urethral smooth muscles.
53
MALE REPRODUCTIVE
ABNORMALITIES
• CRYPTORCHIDISM (UNDESCENDED
TESTES)
– THE DESCENT OF TESTES IS INCOMPLETE IN
10% OF NEONATES
– SPONTANEOUS DESCENT OCCURS LATER
– INCIDENCE: 2% AT INFANCY & 0.3% AFTER
PUBERTY
– COMPLICATIONS: INCREASED INCIDENCE OF
TESTICULAR MALIGNANCIES & INFERTILITY.
54
Testosterone /effects
Synthesis of the male sex hormones in Leydig
cells of the testis. P450SSC, 3b-DH, and
P450c17 are the same enzymes as those
needed for adrenal steroid hormone
synthesis. 17,20-desmolase is the same as
17,20-lyase of adrenal hormone synthesis..
LH & FSH during life of a woman
HL: FSH>LH
Follicles
• At 20th week …..20mil
• At birth …………1-2 mil
• At puberty ……..300-400k
• During reproductive period..400-500
Uterine cycle
• Proliferative
• Secretory
• Ischemic
• Bleeding
Estrogen in proliferation phase
• Cell proliferation in endometrium
• Growth of ER & mitochondria in endometrium
• Increase glycogen storage
• Endometrial glands
• Dilation of arteries and coiled
• Increase in progesterone receptors
• Increase sensitivity & contractility of myometrium
Secretory phase
• Secretion of mucus
• Continue to proliferation
• Edema of endometrium
• Decrease contraction of myometrium
Menstrual cycle
Ovarian cycle
• Follicular phase
• Preovulatory phase
• Ovulatory phase
• Luteal phase
• Luteolysis phase
Steroidogenesis in ovary
Follicle graaf
• Theca interna is rich in Scc450(desmolase)
• Theca interna cells have LH receptors
• Granulosa cells are rich in aromatase
• Granulosa cells have LH & FSH receptors
Synthesis of the major female sex hormones in the ovary. Synthesis of testosterone and
androstenedione from cholesterol occurs by the same pathways as indicated for
synthesis of the male sex hormones.
Hohlweg effect
• Critical plasma concentration for estrogen
– 200pg/ml
– For 36 hrs
– No response to 100pg/ml
• Increase GnRH receptor on gonadotrops (est &
PGE2)
• Increase the enzymatic activity of
gonadotrops(est)
• Increase amplitude & frequency of GnRH(est &
PGE2)
PGs & follicular rupture
Ovulation
• Androgen to estrogen microenvironment
• More FSH receptors
• Hohlweg effect
• Less OMI concentration
• Plasminogen activator
• Plasmin
• Fibrinolysin
• Collagenase
• Inhibin
• FSH & LH…..increase in cAMP
• Prostaglandin F2α( 2-5 hrs before ovulation)
– Completion of first miosis
– Contraction of ovarian smooth muscles
• Oxytocin
Ovulation
Luteal phase
• Progesterone secretion
• Negative Fern test
• LH support
• Maximum activity: 6-8 days after ovulation
Luteolysis
• PGF2α:
– Reduction in blood flow of corpus luteum
– Increase estrogen secretion
– Reduce response of corpus luteum to LH
– Increase OT secretion from CL
Menstrual cycle
Capacitation
• Remove of HMW glycoprotein (polylactoseamine) &
peptides
• Whiplash-like pattern of hyperactivation of sperm
• Removing sterol & cholesterol from the surface
• Rearrangement of surface molecules
• Increase permeability to calcium
• Hyaloronidase activity
• Galactosyl-transferase activity
Acrosome reaction
• Calcium entrance- Ca-cal
• Increase cAMP
• Activation of phospholipaseA2
• Increasing lysophospholipids
• Adhesion
• pH: 5.2 to 7:00
• Segmentation of acrosome
Syngamy
• After enter the sperm, 2nd polar body
• After 30 min, disperse of sperm nucleus
• After 6-8 hrs, pronucleus & syngamy
• After 27-43 hrs, first division
Origin of testosterone in women
Factors affecting SHBG
Stimulator Inhibitors
• Estrogen • Progestins (except OH-
• Hyperthyroidism prog)
• Ageing • GH
• Glucocorticosteroids
• Hypothyroidism
Relation of MCR of steroids & affinity to SHBG
DHEA-S concentration versus age
Distribution of plasma testosterone &
estadiol
Aromatase activity in
• Muscle (25-30% in normal conditions)
• Adipose tissue
• Skin fibroblasts
• Hair follicles
• Brain
Aromatase
Strogens
• Estradiol; 95% by ovary
• Estrone; peripheral conversion
• In normal women: E2/E1 >1