REPRODUCTIVE ENDOCRINOLOGY OF THE MALE

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1 Reproductive Biotechnologies Andrology I REPRODUCTIVE ENDOCRINOLOGY OF THE MALE Prof. Alberto Contri REPRODUCTIVE ENDOCRINOLOGY OF THE MALE SPERMATOGENESIS AND REPRODUCTIVE BEHAVIOR RELATED TO THE ACTIVITY OF THE HYPOTHALAMUS-PITUITARY-TESTIS AXIS ANATOMICALLY, FAR FROM THE REPRODUCTIVE TRACT SECRETION OF SPECIFIC HORMONES THAT ACT ON THE GONAD CONTROL MECHANISM RELATED TO THE SECRETION OF HORMONES IN THE TESTIS ALSO LOCAL ACTIVITY OF THE HORMONES (AUTOCRINE/PARACRINE SYSTEM) 1

2 REPRODUCTIVE ENDOCRINOLOGY OF THE MALE HPT axis Secretion of GnRH (preoptic area) Release of LH and FSH (anterior pituitary gland) Testicular synthesis and release of androgens and estrogens (testosterone and others) Other hormones prolactine, GH, insuline 2

3 PULSATILE RELEASE OF GNRH BY GNRH PULSE GENERATOR NETWORK OF GNRH NEURONS BY SYNAPSES DIFFERENT STIMULI GNRH RELEASED IN THE HP PORTAL SYSTEM AS RESULT, SECRETION OF LH AND FSH LH FSH 3

4 LH AND FSH ACT TO REGULATE THE GONADAL FUNCTION IN-VITRO LH STIMULATE THE SYNTHESIS AND THE RELEASE OF THE ANDROGENS (AND ESTROGENS) BY THE LEYDIG CELLS FSH INDUCE THE RELEASE OF INHIBIN, ACTIVIN NAD OTHER MINOR MOLECULES FROM THE SERTOLI CELLS TESTOSTERONE ACT ON THE HYPOTHALAMUS NEGATIVE FEEDBACK ESTROGENS, 17-Β-ESTRADIOL ACT ON THE PITUITARY GLAND GNRH NEURONS LACK OF ESTROGENS RECEPTOR-ALPHA ROLE OF THE KISSPEPTIN SYSTEM 4

5 KISSPEPTIN SYSTEM SYSTEMIC SECRETION OF KISSPEPTIN HYPOTHALAMIC DECAPEPTIDE HIGHLY STUDIED DURING PUBERTY MODULATION OF THE GNRH KISSPEPTIN DISCOVERED BY STUDIES ON MELANOMA: DETECTION OF THE KISS I GENE KISSPEPTINA LINK THE ORPHAN RECEPTOR GPR54 KISS I R 5

6 Arcuate nucleus Infundibular nucleus Rostral preoptic area Rostral preoptic area Median eminence KISSPEPTIN EXOGENOUS ADMINISTRATION HAVE A DOSE-DEPENDENT EFFECT ON LH FSH 6

7 KISSPEPTIN ACT DIRECTLY ON THE PITUITARY GLAND INDIRECTLY VIA THE GNRH NEURONS TESTOSTERONE CRUCIAL IN THE SPERMATOGENESIS (SYNERGIC ACTIVITY OF FSH) ESTROGENS ALSO IMPLICATED IN THE MAINTENANCE OF THE SPERMATOGENESIS NOT CLEAR THE ACTIVITY IN THE ADULT SEEMED CRUCIAL DURING THE PUBERTY PRESENCE OF AROMATASES AND RECEPTORS IN THE CELLS OF THE TESTIS HIGH CONCENTRATION IN THE SEMINAL PLASMA MODULATION OF THE LEYDIG CELL GROWTH AND OF STEROIDOGENESIS 7

8 Local endocrinology of the testis LOCAL ACTIVITY OF THE TESTIS MODULATED BY AUTOCRINE/PARACRINE SYSTEM NETWORK BETWEEN DIFFERENT CELLULAR TYPES AIM: COORDINATION AND MODULATION OF THE SPERMATOGENESIS Local endocrinology of the testis AUTOCRINE: SECRETIONS MODULATE THE ACTIVITY OF THE SAME CELL PARACRINE: SECRETIONS MODULATE THE ACTIVITY OF DIFFERENT NEAR CELLS 8

9 Autocrine/paracrine system COMMUNICATION SYSTEM BETWEEN GERM CELLS AND ENDOCRINE OR SUPPORTIVE CELLS IMPLICATIONS IN THE SPERMATOGENETIC CYCLE TRIGGERED BY THE AUTONOMIC NERVOUS SYSTEM ENDOCRINE CONTROL ON SEXUAL BEHAVIOUR SEXUAL AROUSAL ERECTION AND EJACULATION DETUMESCENCE 9

10 STUDIED ESPECIALLY IN THE PRIMATES AND LABORATORY ANIMALS FEW DATA IN THE DOMESTIC ANIMAL DIFFERENT BEHAVIOUR DURING THE MATE IN DIFFERENT SPECIES REPRODUCTIVE ENDOCRINOLOGY OF THE STALLION DURING THE MATE EVALUATION OF DIFFERENT HORMONES OXYTOCIN AND VASOPRESSIN PROSTAGLANDINS F2 ALPHA LH TESTOSTERONE ESTROGENS ESTRONE SULFATE 10

11 INCREASE OF THE OXYTOCIN AT EJACULATION ROLES OF THE OXYTOCIN CONTRACTION OF THE URETHRA DURING EJACULATION POSSIBLE ROLE IN THE CENTRAL ACTIVITY OF THE ANS ACTIVITY IN THE FEMALE CONTRACTION OF THE UTERUS AUTOCRINE/PARACRINE TESTICULAR SYSTEM 11

12 INCREASE OF THE PGF AT EJACULATION AND FURTHER INCREASE AFTER ROLES OF THE PGF STIMULATION OF THE SUPRAOCTIC NUCLEUS (RELEASE OF OX AND VAS) CONTRACTION OF THE SMOOTH MUSCULATURE ACTIVITY DURING THE DETUMESCENCE SMOOTH MUSCULATURE CONTRATION OF THE CAVERNOUS TISSUE 12

13 STEROIDS ANDROGENS TESTOSTERONE SEXUAL BEHAVIOR AND AROUSAL ACTIVITY AT SPINAL LEVEL SECRETION OF NEUROMEDIATORS INVOLVED IN THE ERECTION ESTROGENS INDUCE THE PRODUCTION OF NITRIC OXIDE DOPAMINE RELEASE (MEDIAL PREOPTIC AREA) AROUSAL 13