PT  - JOURNAL ARTICLE
AU  - Hugo Salais-López
AU  - Carmen Agustín-Pavón
AU  - Enrique Lanuza
AU  - Fernando Martínez-García
TI  - The maternal hormone in the male brain: sexually dimorphic distribution of prolactin signalling in the mouse brain
AID  - 10.1101/333161
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 333161
4099  - http://biorxiv.org/content/early/2018/10/01/333161.short
4100  - http://biorxiv.org/content/early/2018/10/01/333161.full
AB  - Research of the central actions of prolactin is virtually restricted to females, but this hormone has also documented roles in male physiology and behaviour. Here, we provide the first description of the pattern of prolactin-derived signalling in the male mouse brain, employing the immunostaining of phosphorylated signal transducer and activator of transcription 5 (pSTAT5) after exogenous prolactin administration. Next, we explore possible sexually dimorphic differences by comparing pSTAT5 immunoreactivity in prolactin-supplemented males and females. We also assess the role of testosterone in the regulation of central prolactin signalling in males by comparing intact with castrated prolactin-supplemented males.Prolactin-supplemented males displayed a widespread pattern of pSTAT5 immunoreactivity, restricted to brain centres showing expression of the prolactin receptor. Immunoreactivity for pSTAT5 was present in several nuclei of the preoptic, anterior and tuberal hypothalamus, as well as in the septofimbrial nucleus or posterodorsal medial amygdala of the telencephalon. Conversely, non-supplemented control males were virtually devoid of pSTAT5-immunoreactivity, suggesting that central prolactin actions in males are limited to situations concurrent with substantial hypophyseal prolactin release (e.g. stress or mating). Furthermore, comparison of prolactin-supplemented males and females revealed a significant, female-biased sexual dimorphism, supporting the view that prolactin has a preeminent role in female physiology and behaviour. Finally, in males, castration significantly reduced pSTAT5 immunoreactivity in some structures, including the paraventricular and ventromedial hypothalamic nuclei and the septofimbrial region, thus indicating a region-specific regulatory role of testosterone over central prolactin signalling.Abbreviations3Vthird ventricleAADanterior amygdaloid area, dorsal partAC/ADPanterior commissural nucleus/anterodorsal preoptic nucleus region ac anterior commissureAcbnucleus accumbensACoanterior cortical amygdaloid nucleus AHi amygdalohippocampal areaAHPanterior hypothalamic area, posterior part Aq aqueduct (Sylvius)Arcarcuate hypothalamic nucleus AVP arginine-vasopressinAVPeanteroventral periventricular nucleus Bar Barrington’s nucleusBLAbasolateral amygdaloid nucleus, anterior part BLV basolateral amygdaloid nucleus, ventral part BMP basomedial amygdaloid nucleus, posterior partBSTIAbed nucleus of the stria terminalis, intraamygdaloid division BSTLD bed nucleus of the stria terminalis, lateral division, dorsal part BSTLP bed nucleus of the stria terminalis, lateral division, posterior part BSTLV bed nucleus of the stria terminalis, lateral division, ventral part BSTMA bed nucleus of the stria terminalis, medial division, anterior partBSTMVbed nucleus of the stria terminalis, medial division, ventral partBSTMPIbed nucleus of the stria terminalis, medial division, posterointermediate part BSTMPL bed nucleus of the stria terminalis, medial division, posterolateral part BSTMPM bed nucleus of the stria terminalis, medial division, posteromedial partcccorpus callosumCecentral amygdalaCeCcentral amygdaloid nucleus, capsular part CeL central amygdaloid nucleus, lateral division CeM central amygdaloid nucleus, medial division CPu caudate putamen (striatum)CRFcorticotropin-releasing factor CxA cortex-amygdala transition zone D3V dorsal third ventricleDEndorsal endopiriform nucleus Dk nucleus of DarkschewitschDLGdorsal lateral geniculate nucleus DLPAG dorsolateral periaqueductal grey DM dorsomedial hypothalamic nucleus DMPAG dorsomedial periaqueductal grey DMTg dorsomedial tegmental areaDpGdeep grey layer of the superior colliculus DpMe deep mesencephalic nucleusDpWhdeep white layer of the superior colliculus DR dorsal raphe nucleusDTgdorsal tegmental nucleus f fornixfifimbria of the hippocampusHDBnucleus of the horizontal limb of the diagonal band I intercalated nuclei of the amygdalaicinternal capsuleIFinterfascicular nucleusInCinterstitial nucleus of CajalInGintermediate grey layer of the superior colliculus InWh intermediate white layer of the superior colliculusIPACinterstitial nucleus of the posterior limb of the anterior commissure La lateral amygdaloid nucleusLAlateroanterior hypothalamic nucleus LC locus coeruleusLDTglaterodorsal tegmental nucleus LGP lateral globus pallidusLHlateral hypothalamic area LHb lateral habenular nucleus lo lateral olfactory tractLOTnucleus of the lateral olfactory tract LPAG lateral periaqueductal greyLPBClateral parabrachial nucleus, central part LPBD lateral parabrachial nucleus, dorsal part LPBE lateral parabrachial nucleus, external part LPBI lateral parabrachial nucleus, internal part LPBV lateral parabrachial nucleus, ventral part LSD lateral septal nucleus, dorsal partLSIlateral septal nucleus, intermediate part LSV lateral septal nucleus, ventral partLVlateral ventricleMCLHmagnocellular nucleus of the lateral hypothalamus mcp middle cerebellar peduncleMCPOmagnocellular preoptic nucleus ME median eminenceMeAmedial amygdaloid nucleus, anterior partMePDmedial amygdaloid nucleus, posterodorsal part MePV medial amygdaloid nucleus, posteroventral part MGD medial geniculate nucleus, dorsal partMGMmedial geniculate nucleus, medial part MGP medial globus pallidusMGVmedial geniculate nucleus, ventral part MHb medial habenular nucleusmlmedial lemniscusmlfmedial longitudinal fasciculus MnPO median preoptic nucleus MnR median raphe nucleusMPAmedial preoptic areaMPBmedial parabrachial nucleusMPBEmedial parabrachial nucleus, external part MPO medial preoptic nucleusMSmedial septal nucleus mt mammilothalamic tract MTu medial tuberal nucleusMZMGVmarginal zone of the medial geniculate opt optic tractOToxytocinoxoptic chiasmPaparaventricular nucleusPaLMparaventricular nucleus, lateral magnocellular part PaMM paraventricular nucleus, medial magnocellular part PaPO paraventricular nucleus, posterior partPaVparaventricular nucleus, ventral partPAGperiaqueductal greyPe periventricular hypothalamic nucleusPeFperifornical nucleusPHposterior hypothalamic areaPILposterior intralaminar thalamic nucleus Pir piriform cortexPLCoposterolateral cortical amygdaloid nucleus PnC pontine reticular nucleus, caudal partPnOpontine reticular nucleus, oral part PnR pontine raphe nucleusPnVpontine reticular nucleus, ventral partPoTposterior thalamic nuclear group, triangular part PP peripeduncular nucleusPRLprolactinPSThparasubthalamic nucleusPVparaventricular thalamic nucleusPVAparaventricular thalamic nucleus, anterior part RCh retrochiasmatic areaRMgraphe magnus nucleuss5sensory root of the trigeminal nerve SCh suprachiasmatic nucleusSFiseptofimbrial nucleus SFO subfornical organSGsuprageniculate thalamic nucleus SI substantia innominataSLEAsublenticular extended amygdala sm stria medullaris of the thalamus SNC substantia nigra, pars compacta SNR substantia nigra, reticular part SO supraoptic nucleusSPasubparaventricular zone of the hypothalamusststria terminalisSThsubthalamic nucleusSubCDsubcoeruleus nucleus, dorsal part SubCV subcoeruleus nucleus, ventral part SuM supramammillary nucleusTeterete hypothalamic nucleus Tu olfactory tubercleVEnventral endopiriform nucleus VLG ventral lateral geniculate nucleusVLGMCventral lateral geniculate nucleus, magnocellular part VLGPC ventral lateral geniculate nucleus, parvicellular part VLPAG ventrolateral periaqueductal greyVLPOventrolateral preoptic nucleusVMHventromedial hypothalamic nucleusVMHcventromedial hypothalamic nucleus, central part VMHdm ventromedial hypothalamic nucleus, dorsomedial part VMHvl ventromedial hypothalamic nucleus, ventrolateral part VMPO ventromedial preoptic nucleusVOLTvascular organ of the lamina terminalis VP ventral pallidumVReventral reuniens thalamic nucleus vsc ventral spinocerebellar tractVTAventral tegmental area ZI zona incerta