STEROID EFFECTS ON SDN-POA

The sexually dimophic nucleus of the preoptic area (SDN-POA) of rat is larger in maleThe sexually dimophic nucleus of the preoptic area (SDN-POA) of rat is larger in malethan in female.than in female.Perinatal treatments of females with T or DES (E2 analogue) induce an increase of thePerinatal treatments of females with T or DES (E2 analogue) induce an increase of thevolume of SDN in femalesvolume of SDN in females

Influences of the perinatal hormonal environment on the Influences of the perinatal hormonal environment on the volume of the SDN-POAvolume of the SDN-POA

TP D-4: females with single injection of 1.25mg testosterone propionate on day 4TP D-4: females with single injection of 1.25mg testosterone propionate on day 4PROL TP: females with daily injections of TP for a prolonged period (till day 10)PROL TP: females with daily injections of TP for a prolonged period (till day 10)EB-D2: females with single injection of 100 µg estradiol benzoate on day 2EB-D2: females with single injection of 100 µg estradiol benzoate on day 2PROL DES: females with daily injections of EB for a prolonged period (till day 10)PROL DES: females with daily injections of EB for a prolonged period (till day 10)GX D-1: gonadectomized males on day 1GX D-1: gonadectomized males on day 1TP D-2: gonadectomized males on day 1 + single injection of 100µg TP on day 2TP D-2: gonadectomized males on day 1 + single injection of 100µg TP on day 2TFM: males with testicular feminizing mutationTFM: males with testicular feminizing mutation

O: adul rats pre- (16 day) and postnatally (for 10 days after birth) treated with sesame oil CA: adul rats pre- and postnatally treated with cyproterone acetate (androgen antagonist)TA: adul rats pre- and postnatally treated with tamoxifen (estrogen antagonist)Sacrifice: 2 months

Endocrine effectsEndocrine effects- Cyproterone induces a cyclic Cyproterone induces a cyclic release of gonadotropins in malerelease of gonadotropins in male- Tamoxifen induces anovulation in Tamoxifen induces anovulation in femalefemale

Tamoxifen reduces the volume Tamoxifen reduces the volume of SDN only in male of SDN only in male

DEVELOPMENT AND DEVELOPMENT AND DIFFERENTIATION OF THE SDN DIFFERENTIATION OF THE SDN ARE UNDER CONTROL OF ARE UNDER CONTROL OF ESTROGENSESTROGENS

(Dohler et al, Neuroendocrinol, 1986)

Sexual Differentiation of the BrainSexual Differentiation of the Brain

The undifferentiated brain is basically female: the default structureThe undifferentiated brain is basically female: the default structure Perinatal testosterone transforms it into the male structure via Perinatal testosterone transforms it into the male structure via

estradiolestradiol The transformation is governed by aromatase (TThe transformation is governed by aromatase (TE) which is E) which is

limiting the production of E2limiting the production of E2 Alpha-fetoprotein prevents masculinization of femalesAlpha-fetoprotein prevents masculinization of females

Undifferentiated brain

Masculine brain

Female brain

Perinatal testosteronePerinatal testosterone

Estradiol

aromatase

CLASSIC MODELCLASSIC MODEL

Masculinization of the circuits dipends by gonadal Masculinization of the circuits dipends by gonadal hormone expositionhormone exposition

Female circuits develop in absence of hormonesFemale circuits develop in absence of hormones

Behavioral Sexual DifferentiationBehavioral Sexual Differentiation“Masculinization” “Masculinization”

+/- = display mounts+/- = display mountsPink = normal femalePink = normal femaleWhite = normal maleWhite = normal maleBlack = female treated with perinatal androgenBlack = female treated with perinatal androgenYellow = male castrated on PN1Yellow = male castrated on PN1

♀♀ ♂♂ ♂♂♀♀+T+T

Beach et al. (rats):Beach et al. (rats):

+/- + + -+/- + + -

TESTOSTERONE ROLE IN MALETESTOSTERONE ROLE IN MALE

In male rodents T secreted In male rodents T secreted by testes enters into the by testes enters into the brain and it is aromatized brain and it is aromatized in E2.in E2.E2 binds estrogen receptors E2 binds estrogen receptors and controls genic and controls genic expression in order to expression in order to masculinize and defeminize masculinize and defeminize the nervous circuits the nervous circuits controlling the sexual controlling the sexual behavior.behavior.

The real The real motormotor of the of the masculine differentiation masculine differentiation of the brain is the of the brain is the locally locally produced estradiolproduced estradiol

…… …… following ……….following ……….

The testosterone and its metabolites are active The testosterone and its metabolites are active during a specific period (during a specific period (critical periodcritical period) and they ) and they induce the differentiation of both brain and behavior.induce the differentiation of both brain and behavior.

Organizational effectOrganizational effect

Irreversible changes of the sexual behaviorIrreversible changes of the sexual behavior

Irreversible changes in some nervous circuitsIrreversible changes in some nervous circuits

CONCLUSIONSCONCLUSIONS In the preoptic area there is a nerve network that regulates influence of In the preoptic area there is a nerve network that regulates influence of steroids on male reproductive functions steroids on male reproductive functions

The central part of the circuit is the medial preoptic nucleus (MPN), that The central part of the circuit is the medial preoptic nucleus (MPN), that inside contains the sexually dimorphic nucleus (SDN)inside contains the sexually dimorphic nucleus (SDN)

The circuit is interposed between the sensitive and the motor The circuit is interposed between the sensitive and the motor componentscomponents

Lesions of the preoptic area may induce a significative decrease of male Lesions of the preoptic area may induce a significative decrease of male sexual behaviorsexual behavior