Sexual Differentiation of Gonadotropin Patterns

The original experiments, done by Witschi and his associates,on sexual differentiation of pituitary gonadotropins weie interpietedas demonstrating the contrasting effects of testes on the subsequentoutput of luteimzing hormone (LH) and interstitial cell stimulatinghormone (ICSH). The subsequent demonstration that these twohormones were identical has led to a theory that testes alterthe hypothala mic centeis which control the cyclic release ofLH "Masculinization of the female hypothalamic pituitary axishas been claimed following neonatal treatment with steroids".However, true sex reversal of gonadotiopin patterns has neitherbeen demon stiated, the male pattern has not yet been clearlydenned Consistent high levels of blood and pituitary folliclestimulating hormone (FSH) appear to be at least two characteristicsof the male pattern, and neither can be induced in lemales byneonatal treatment with testosterone propionate. Furthermore,castration of males at bnth with concomitant ovanan implinldtion,does not appear to remove the male pattern of high FSH. Consideringthat we understand so little regarding gonadotropin patternsin males, we cannot assume that this pattern can be inducedsimply by pie or postnatal steroid trealment. Considerably moredata on the positive and negative feedback effects of steroids,and steroid combinations, on TSH, LH, and piolictin in bothmales and females, will be requned before a meaningful conceptof sexual differentiation cin be formulated     

Neuroendocrine Systems and Avian Sexual Differentiation

Sexual differentiation of the endocrine and behavioral componentsof the avian reproductive system occurs throughout embryonicdevelopment, initiating some of the early cellular events thatform the central nervous system (CNS) and culminating in theorganization of male or female neuroendocrine responses. Earlycellular events have been studied intensively in recent yearsand these developmental processes appear to involve specificgrowth factors in the development of certain tissues. Subsequentto cellular differentiation, primordial germ cells migrate tothe appropriate anatomical location and contribute to the developmentof the single ovary or testes; steroidogenesis begins soon thereafter.Other portions of the hypothalamo-pituitary-gonad (HPG) axisalso appear during early embryonic development with migrationof the gonadotropin-releasing hormone (GnRH) neurons from theolfactory region of the CNS to the midbrain and separate formationof the pituitary gland. The gonadal steroid hormones affectdevelopment of accessory sex structures as well as the laterorganization of neuroendocrine regulatory systems and secondarysex characteristics. Manipulation of steroids during embryonicand early posthatch periods results in altered endocrine andbehavioral responses in adult birds. There are marked speciesdifferences in the timing of these events, especially when precocialand altricial species are compared. Altricial species hatchin a less developed state and as such are more dependent onparental care. Of necessity, the precocial species must be capableof feeding and other motor capabilities at hatch and coincidentallytheir other physiological systems also appear to be more matureat this time. Finally, there is the separate issue of song birdsversus those avian species that do not have elaborate learnedsongs. It appears that most of the species with elaborate neuralcircuitry responsible for song are altricial. This may benefitthem from the standpoint of gaining more time and contact withthe parents to enable them to learn the appropriate song. Thereare also hormonal and neuroendocrine components critical inthe process of song development. Finally, the effects of environmentalfactors, such as endocrine disrupting chemicals take on addedsignificance when viewed in the context of exerting permanentorganizational effects which are likely to alter endocrine andbehavioral components of reproduction in the adult     

Genetically Triggered Sexual Differentiation of Brain and Behavior

The dominant theory of sexual differentiation of the brain holds that sex differences in brain anatomy and function arise because of the action of gonadal steroids during embryonic and neonatal life. In mammals, testicular steroids trigger masculine patterns of neural development, and feminine patterns of neural development occur in the absence of such testicular secretions. In contrast, gonadal differentiation in mammals is not initiated by hormonal mechanisms, but is regulated by the action of gene products such as SRY, a testis-determining gene on the Y chromosome. This paper argues that such genetic, nonhormonal signals may also trigger specific examples of sexual differentiation of the brain. This thesis is supported by two arguments. The first is that “direct genetic” (i.e., nonhormonal) control of sexual differentiation may be as likely to evolve as hormonal control. The second line of argument is that neural and nonneural dimorphisms have already been described that are not well explained by classical theories of steroid-dependent sexual differentiation and for which other factors need to be invoked.     

Sexual Differentiation in Volvox aureus*

SYNOPSIS. The complete life history of a homothallic, dioecious strain of Volvox aureus was studied in axenic culture. Asexual reproduction occurs by repeated division of specialized reproductive cells (gonidia), inversion of the resultant mass of cells to form daughter colonies, and subsequent morphologic differentiation of new gonidia in these daughters. Male colonies lack gonidia; however, the posterior 2/3 of the cells in a colony function as male initials each of which enlarges, divides, and undergoes rudimentary inversion to form a packet of 32 biflagellate sperm. Evidence was presented for the homology of eggs and undivided gonidia. The penetration of young vegetative colonies by sperm and the subsequent formation of apparent zygotes in these colonies was described and figured. Zygote germination, including division and inversion of the germling, was described; the cytological nature of the zygote divisions was not determined. A substance, MIS, in filtrates of sexual cultures induced differentiation of male colonies; a bioassay for it was perfected. Bioassay colonies show a differential susceptibility to male induction by MIS which is a function of the particular stage of development; colonies 48 hr after release from parentals are optimally susceptible. MIS was reasonably stable to heat, non-dialyzable, and Sephadex gel filtration indicated a molecular weight > 200,000. MIS activity is destroyed by trypsin and pronase but is unaffected by chymotrypsin. MIS was successfully concentrated ～37-fold by the Carbowax method. The patterns of differentiation in other species of Volvox are described and possibilities discussed for studies of cellular differentiation in the genus as a whole.     

Genetic Control of Sexual Differentiation in Humans

The current literature results on genetic control of sex differentiation and morphogenesis of the human reproductive system are reviewed. Several examples of the nosologic forms caused by mutations in the genes analyzed are considered.     

Hormonal Control of Sexual Differentiation and Reproduction in Crustacea

SYNOPSIS. Sexual differentiation in malacostracan Crustaceais controlled by the androgenic gland hormone (AGH). In males,the primordial androgenic glands (AG) develop and AGH inducesmale morphogenesis. In females, the primordial AG does not developand the ovaries differentiate spontaneously. Implantation ofthe AG into females yields various results, showing that thesensitivity to AGH differs with the species and the receptiveorgans. Purified AGH of the isopod Armadillidium vulgare consistsof at least two molecular forms, which exist as monomeric proteinswith molecular weights of 17,000 ± 800 and 18,300 ±1,000 Da and with isoelectric points of about 4.5 and 4.3, respectively.The antiserum raised against purified AGH makes it possibleto measure AGH activity by immunoassay. Neurohormones control male and female reproduction. In males,they are involved in the maintenance of the male germinativezone and the control of AG activity. In females, the secondaryvitellogenesis is controlled by the vitellogenesis-inhibitinghormone (VIH) and the vitellogenesis- stimulating hormone (VSH).VIH isolated from the lobster Homarus americanus is a peptidewith a molecular weight of 9,135 Da and shows homology to thecrustacean hyperglycemic hormone and moltinhibiting hormone.Involvement of the molting hormone and the juvenile hormone-likecompound in the secondary vitellogenesis have also been suggested.In the amphipod Orchestia gammarella, the vitellogenesis- stimulatingovarian hormone (VSOH) seems to control vitellogenin synthesis     

Prenatal Stress and Sexual Differentiation of Monoaminergic Brain Systems

This review considers published data and results of the authors' studies of prenatal (maternal) stress-induced disturbances in the sexual differentiation of monoaminergic systems in sexually dimorphic brain regions. The significant role of glucocorticoid hormones as crucial humoral factors mediating the above effects of prenatal stress is emphasized. The involvement of enzymes, providing synthesis and metabolic transformations of biogenic monoamines in the brain, in modifications of the prenatal stress-related hormonal/transmitter imprinting of the developing brain is discussed in particular.     

Multilocus and Multitrait Measures of Differentiation for Gene Markers and Phenotypic Traits

Multilocus measures of differentiation taking into account gametic disequilibrium are developed. Even if coupling and repulsion heterozygotes cannot be separated at the multilocus level, a method is given to calculate a composite measure of differentiation (CF(st)) at the zygotic level, which accounts for allelic associations combining both gametic and nongametic effects. Mean and maximum differentiations may be relevant when multilocus measures are computed. Maximum differentiation is the highest eigenvalue of the F(st) matrix, whereas mean differentiation corresponds to the mean value of all eigenvalues of the F(st) matrix. Gametic disequilibrium has a stronger effect on maximum differentiation than on mean differentiation and takes into account the anisotropy that may exist between within- and between-population components of disequilibria. Multilocus mean and maximum differentiation are calculated for a set of 81 Quercus petraea (sessile oak) populations assessed with eight allozyme loci and two phenotypic traits (bud burst and height growth). The results indicate that maximum differentiation increases as more loci (traits) are considered whereas mean differentiation remains constant or decreases. Phenotypic traits exhibit higher population differentiation than allozymes. The applications and uses of mean and maximum differentiations are further discussed.     

Evidence for Sexual Differentiation of Glia in Rat Brain

It is well established that gonadal steroids mediate sexual differentiation of the brain via direct effects on neurons during a restricted critical period. In addition, estrogen can influence glial morphology in the adult brain, andin vitrostudies suggest estrogen induces glial differentiation. However, there is a lack ofin vivoevidence for steroid effects on glia during the critical period. We report here a hormone-mediated sexual differentiation of arcuate glia as early as Postnatal Day 1. Using glial fibrillary acidic protein immunoreactivity (GFAP-ir), we compared the responsiveness of astroglia in the rat arcuate nucleus among five hormonally different groups. The results indicate increased GFAP-ir cell surface area 24 hr after hormonal manipulation in castrate males compared to intact males, intact females (ANOVA;P< 0.01), and females injected with testosterone propionate (50 μg; ANOVA;P< 0.05). However, astroglia in intact males extended their processes significantly greater distances from the cell body compared to all other treatment groups (ANOVA;P< 0.01). The GFAP-ir cells were categorized into four distinct classes ranging from a simple bipolar to a fully stellate morphology. The frequency distribution of classes varied between groups with more stellate cells found in intact males. Finally, these sex differences in arcuate glia persisted into adulthood. We hypothesize that during the critical period, testosterone, or its metabolite estrogen, induce sexual differentiation of glia. We further hypothesize that in females glial cells remain partially undifferentiated and this may be important to glial plasticity seen in adult female arcuate.     

Gonadal Hormones and Brain Development: Cellular Aspects of Sexual Differentiation

Sexual differentiation of the neural control of reproductivefunction with respect to both gonadotropin secretion and sexualbehavior is thought to result from exposure of the brain totesticular androgens during a very restricted or critical periodof CNS differentiation and development, when the tissue is competentto respond to the hormone, and after which it is refractoryor responds in a reversible manner. This paper reviews the cellularaspects of sexual differentiation with particular emphasis onthe morphological expression of the gonadal hormonal effectsin the adult brain. It presents experimental evidence for themorphogenetic basis for the observed steroid effects by showinghow the addition of steroid to undifferentiated hypothalamiccultures produces a selective neuritic response that is steroid-dependent.These results suggest that since afferent axonal input and temporalfactors are critical for dendritic and synaptic differentiation,steroid-induced variations in neuritic development could resultin gender-specific responses seen in sexual differentiationof reproductive function.     

Sexual Traits as Quality Indicators in Lekking Male Great Bustards

We studied the development of two sexual traits, whiskers and neck plumage, in relation to sexual selection in 41 free‐living great bustard, Otis tarda, males radio‐tracked at nine leks in central Spain in 1998–2001. During the pre‐breeding male–male competition period (Feb.) prior to female arrival, number and length of whiskers correlated with weight, but not with body size or age. Whiskers may thus have evolved as an intrasexual indicator of weight, which in the absence of other weapons in this species is decisive in male–male combats. Signalling through whiskers contributes to minimizing dangerous aggressive interactions in the lek. During the mating period (Apr.), both whisker and neck development were correlated with weight and age. Males reaching higher expression of both traits exhibited higher display intensity, a more prolonged display period through the mating season, and a higher estimated mating success. Moreover, interannual changes in a male’s expression of both traits were associated with changes in its display intensity and estimated mating success. Our results resolve earlier debates and contradictory results from previous authors, suggesting that these two secondary sexual traits, whiskers and neck, may function as reliable indicators of age and weight, the two main factors determining social rank of males in great bustard leks, during both rival assessment and mate choice. Their dual functions provide support for the pre‐existing trait and redundant signal hypotheses and suggest that multiple ornaments functioning as redundant signals might be more widespread than previously acknowledged.     

Genetically Controlled Hormonal Regulation of Human Sexual Differentiation and Reproductive System Development

Literature data on genetic control of hormonal regulation of sexual differentiation and reproduction system development in humans are reviewed. The conditions caused by mutations of genes for gonadoliberin, gonadotropin, and anti-Mullerian hormone, as well as genes controlling biosynthesis of sexual steroids and the receptors for the latter, are considered.     

Inverted Social Reward: Associations between Psychopathic Traits and Self-Report and Experimental Measures of Social Reward

Individuals with high levels of psychopathic traits tend to undervalue long-term, affiliative relationships, but it remains unclear what motivates them to engage in social interactions at all. Their experience of social reward may provide an important clue. In Study 1 of this paper, a large sample of participants (N = 505) completed a measure of psychopathic traits (Self-Report Psychopathy Scale Short-Form) and a measure of social reward value (Social Reward Questionnaire) to explore what aspects of social reward are associated with psychopathic traits. In Study 2 (N = 110), the same measures were administered to a new group of participants along with two experimental tasks investigating monetary and social reward value. Psychopathic traits were found to be positively correlated with the enjoyment of callous treatment of others and negatively associated with the enjoyment of positive social interactions. This indicates a pattern of ‘inverted’ social reward in which being cruel is enjoyable and being kind is not. Interpersonal psychopathic traits were also positively associated with the difference between mean reaction times (RTs) in the monetary and social experimental reward tasks; individuals with high levels of these traits responded comparatively faster to social than monetary reward. We speculate that this may be because social approval/admiration has particular value for these individuals, who have a tendency to use and manipulate others. Together, these studies provide evidence that the self-serving and cruel social behaviour seen in psychopathy may in part be explained by what these individuals find rewarding.     

Sexual Differentiation of the Brain as a Manifestation of Its Plasticity

This review analyzes the published data and authors' own results on the roles of hormones and neurotransmitters in the formation of structural and functional sex-related dimorphism of the brain within the early ontogenesis period. Proof is presented in favor of the concept that classic neurotransmitters function as inductors of nerve cell differentiation in the process of individual development of the brain. Neurochemical mechanisms of the hormone–transmitter interaction in the process of sexual differentiation of the brain within pre- and/or post-natal periods are considered.     

Factors Influencing the Differentiation of Dopaminergic Traits in Transplanted Neural Stem Cells

1. Our previous studies demonstrated that when neural stem cells (NSCs) of the C17.2 clonal line are transplanted into the intact or 6-hydroxydopamine (6-OHDA) lesioned rat striatum, in most, but not all grafts, cells spontaneously express the dopamine (DA) biosynthetic enzymes, tyrosine hydroxylase (TH), and aromatic L-amino acid decarboxylase (Yang, M., Stull, N. D., Snyder, E. Y., Berk, M. A., and Iacovitti, L. (2002). Exp. Neurol.).2. These results suggested that there were certain conditions which were more conducive to the development of DA traits in NSCs and possibly other neurotransmitter phenotypes.3. In the present study, we modified a number of variables in vitro (i.e. passage number, confluence) and/or in vivo (degree, type, and site of injury) before assessing the survival, migration, and differentiation of engrafted NSCs.4. We found that low confluence cultures were comprised exclusively of flattened polygonal cells, which when transplanted, migrated widely in the brain but did not express TH.5. In contrast, high confluence cultures contained both polygonal cells and an overlying bed of fusiform cells.6. When these NSCs were maintained for 12–20 passages and then transplanted, virtually all engrafted cells in 65% of the grafts expressed TH but not markers of other neurotransmitter systems.7. Importantly, all TH⁺ grafts were accompanied by significant physical damage to the brain while TH^– grafts were not, suggesting that local injury-related factors were also important.8. Of no apparent influence on TH expression, regardless of how cells were grown prior to implantation, was the site of transplantation (cortex or striatum) or the degree of chemical lesion (intact, partial or full).9. We conclude that transplanted NSCs can express traits specifically associated with DA neurons but only when cells are grown under certain conditions in vitro and then transplanted in proximity to injury-induced factors present in vivo.     

Genes Involved in Light Control of Sexual Differentiation in Chlamydomonas Reinhardtii

Gamete formation requires the sequential action of two extrinsic cues, nitrogen deprivation and blue light. The mutants described here are specifically altered in the light-dependent step. Mutations lrg1, lrg3, and lrg4 overcome this light dependence while mutation lrg2 results in a delayed execution of the light-mediated step. The four mutations are linked. The recessive nature of the lrg1, lrg3, and lrg4 mutations implies that they encode elements of negative control in this light response pathway. Analyses of diploids suggest an interaction between the gene products of the mutated loci with a central role for lrg4. The lrg4 mutation is unique also because it overcomes the light dependence of Chlamydomonas zygote germination when present in homozygous form. These data indicate that there are common components in the signal chains that control gametogenesis and zygote germination.     

Common and Distinct Impacts of Autistic Traits and Alexithymia on Social Reward

According to the social motivation hypothesis of autism, individuals with high levels of autistic traits experience reduced levels of reward from social interactions. However, empirical evidence to date has been mixed, with some studies reporting lower levels of social reward in individuals with Autism Spectrum Disorder (ASD), and others finding no difference when compared to typically developing controls. Alexithymia, a subclinical condition associated with the reduced ability to identify and describe one’s own emotions, has been found to account for other affective difficulties observed inconsistently in individuals with ASD. The current study used a nonclinical sample (N = 472) to explore the associations between autistic traits and the value of six types of social reward, as measured by the Social Reward Questionnaire. In addition, we measured alexithymia to assess if this accounted for associations between autistic traits and social reward. There were three main findings. Firstly, higher levels of autistic traits were associated with significantly less enjoyment of admiration and sociability, and adding alexithymia to these models did not account for any additional variance. Secondly, both autistic traits and alexithymia were uniquely associated with reduced levels of enjoyment of prosocial interactions and sexual relationships. Thirdly, autistic traits were associated with higher levels of enjoyment of passivity and negative social potency, but these associations were no longer significant once alexithymia was taken into account, suggesting that co-occurring alexithymia accounted for these apparent associations. Overall, the current findings provide a novel and more nuanced picture of the relationship between autistic traits and social reward.