As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.

How do you feel? Interoception: the sense of the physiological condition of the body.

Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI.

The birth of an intersex child prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques, understanding psychosocial issues and in recognizing and accepting the place of patient advocacy. The Lawson Wilkins Paediatric Endocrine Society (LWPES) and the European Society for Paediatric Endocrinology (ESPE) considered it timely to review the management of intersex disorders from a broad perspective, to review data on longer term outcome and to formulate proposals for future studies. The methodology comprised establishing a number of working groups whose membership was drawn from 50 international experts in the field. The groups prepared prior written responses to a defined set of questions resulting from an evidence based review of the literature. At a subsequent gathering of participants, a framework for a consensus document was agreed. This paper constitutes its final form.

/pdf/consensus-statement-on-management-of-intersex-disorders-1icrsai49n.pdf

Consensus statement on management of intersex disorders

https://www.fertstert.org/article/S0015-0282(08)01392-7/pdf

The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report

Steroidogenesis entails processes by which cholesterol is converted to biologically active steroid hormones. Whereas most endocrine texts discuss adrenal, ovarian, testicular, placental, and other steroidogenic processes in a gland-specific fashion, steroidogenesis is better understood as a single process that is repeated in each gland with cell-type-specific variations on a single theme. Thus, understanding steroidogenesis is rooted in an understanding of the biochemistry of the various steroidogenic enzymes and cofactors and the genes that encode them. The first and rate-limiting step in steroidogenesis is the conversion of cholesterol to pregnenolone by a single enzyme, P450scc (CYP11A1), but this enzymatically complex step is subject to multiple regulatory mechanisms, yielding finely tuned quantitative regulation. Qualitative regulation determining the type of steroid to be produced is mediated by many enzymes and cofactors. Steroidogenic enzymes fall into two groups: cytochrome P450 enzymes and hydroxysteroid dehydrogenases. A cytochrome P450 may be either type 1 (in mitochondria) or type 2 (in endoplasmic reticulum), and a hydroxysteroid dehydrogenase may belong to either the aldo-keto reductase or short-chain dehydrogenase/reductase families. The activities of these enzymes are modulated by posttranslational modifications and by cofactors, especially electron-donating redox partners. The elucidation of the precise roles of these various enzymes and cofactors has been greatly facilitated by identifying the genetic bases of rare disorders of steroidogenesis. Some enzymes not principally involved in steroidogenesis may also catalyze extraglandular steroidogenesis, modulating the phenotype expected to result from some mutations. Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis.

The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.

Despite its critical sociobiological importance, the brain processing of visual sexual stimuli has not been characterized precisely in human beings. We used Positron Emission Tomography (PET) to investigate responses of regional cerebral blood flow (rCBF) in nine healthy males presented with visual sexual stimuli of graded intensity. Statistical Parametric Mapping was used to locate brain regions whose activation was associated with the presentation of the sexual stimuli and was correlated with markers of sexual arousal. The claustrum, a region whose function had been unclear, displayed one of the highest activations. Additionally, activations were recorded in paralimbic areas (anterior cingulate gyrus, orbito-frontal cortex), in the striatum (head of caudate nucleus, putamen), and in the posterior hypothalamus. By contrast, decreased rCBF was observed in several temporal areas. Based on these results, we propose a model of the brain processes mediating the cognitive, emotional, motivational, and autonomic components of human male sexual arousal.

Brain processing of visual sexual stimuli in human males

Brain areas activated in human male sexual behavior have not been characterized precisely. For the first time, positron emission tomography (PET) was used to identify the brain areas activated in healthy males experiencing visually evoked sexual arousal. Eight male subjects underwent six measurements of regional brain activity following the administration of [15O]H2O as they viewed three categories of film clips: sexually explicit clips, emotionally neutral control clips, and humorous control clips inducing positive but nonsexual emotions. Statistical Parametric Mapping was used to identify brain regions demonstrating an increased activity associated with the sexual response to the visual stimulus. Visually evoked sexual arousal was characterized by a threefold pattern of activation: the bilateral activation of the inferior temporal cortex, a visual association area; the activation of the right insula and right inferior frontal cortex, which are two paralimbic areas relating highly processed sensory information with motivational states; and the activation of the left anterior cingulate cortex, another paralimbic area known to control autonomic and neuroendocrine functions. Activation of some of these areas was positively correlated with plasma testosterone levels. Although this study should be considered preliminary, it identified brain regions whose activation was correlated with visually evoked sexual arousal in males.

Neuroanatomical correlates of visually evoked sexual arousal in human males.

Total and unbound testosterone and Delta(4)-androstenedione have been determined in 104 cord blood samples. The same sexual steroids and pituitary gonadotropins have been measured in 46 normal male infants aged 27-348 days and 34 normal female infants aged 19-332 days. In cord blood of female neonates mean total and unbound testosterone was 29.6+/-7.5 and 0.89+/-0.4 ng/100 ml, respectively (mean+/-1 SD); Delta(4)-androstenedione was 93+/-38 ng/100 ml. In male neonates mean plasma total and unbound testosterone was 38.9+/-10.8 and 1.12+/-0.4 ng/100 ml; Delta(4)-androstenedione was 85+/-27 ng/100 ml. In female infants testosterone concentrations remained constant during the 1st yr of life with a mean concentration of 7+/-3 ng/100 ml. Mean unbound testosterone and Delta(4)-androstenedione concentrations were 0.05+/-0.03 and 16.7+/-8.3 ng/100 ml, respectively. Mean plasma levels of follicle-stimulating hormone and luteinizing hormone were 8.7+/-3.3 and 12.9+/-7.7 mU/ml. In male infants mean plasma total testosterone concentration increased to 208+/-68 ng/100 ml from birth to 1-3 mo of age, decreasing thereafter to 95+/-53 ng/100 ml at 3-5 mo, 23.2+/-18 ng/100 ml at 5-7 mo, and reached prepubertal levels (6.6+/-4.6 ng/100 ml) at 7-12 mo. Mean unbound testosterone concentration plateaued from birth to 1-3 mo of age (1.3+/-0.2 ng/100 ml) decreasing to prepubertal values very rapidly. Mean Delta(4)-androstenedione concentration, although progressively decreasing during the 1st yr of life to 11.7+/-4.5 ng/100 ml, was higher than in the female at 1-3 mo of life (34+/-11 ng/100 ml). Mean plasma level of follicle-stimulating hormone was 6.7+/-2.9 mU/ml, and that of luteinizing hormone was 19.7+/-13.5 mU/ml, significantly higher than in the female. There was no correlation between gonadotropin and age or testosterone. The present data demonstrate that the testes are active during the first natal period. It is tempting to correlate this phenomenon to a progressive maturation of the hypothalamo-pituitary-gonadal axis. It is possible that the surge in testosterone occurring the first 3 mo could play a role in the future life pattern of the male human being.

/pdf/hypophyso-gonadal-function-in-humans-during-the-first-year-5ezp9j2kft.pdf

Hypophyso-gonadal function in humans during the first year of life. 1. Evidence for testicular activity in early infancy

Plasma testosterone (T) was measured by a sensitive radioimmunoassay method in 143 normal newborns and infants. In cord blood T levels are significantly higher in male than in female newborns. In male infants there was an increase of T concentration from birth to the 2-3th months of life, followed by a gradual decrease. After the 7th month values observed reached those of prepubertal boys. In females the pattern was very different. T levels dropped rapidly from birth to the second week of life reaching values similar to those of prepubertal girls.

/pdf/evidence-of-testicular-activity-in-early-infancy-4iwyq4tq8w.pdf

Evidence of testicular activity in early infancy

Strong overexpression of anti-Mullerian hormone (AMH) in transgenic mice leads to incomplete fetal virilization and decreased serum testosterone in the adult. Conversely, AMH-deficient mice exhibit Leydig cell hyperplasia. To probe the mechanism of action of AMH on Leydig cell steroidogenesis, we have studied the expression of mRNA for steroidogenic proteins in vivo and in vitro and performed a morphometric analysis of testicular tissue in mice overexpressing the hormone. We show that overexpression of AMH in male transgenic mice blocks the differentiation of Leydig cell precursors. Expression of steroidogenic protein mRNAs, mainly cytochrome P450 17α-hydroxylase/C17–20 lyase (P450c17), is decreased in transgenic mice overexpressing AMH and in AMH-treated purified Leydig cells. In contrast, transgenic mice in whom the AMH locus has been disrupted show increased expression of P450c17. In vitro, but not in vivo, AMH also decreases the expression of the luteinizing hormone receptor. The effect of AMH is explained by the presence of its receptor on Leydig cells. Our results provide insight into the action of AMH as a negative modulator of Leydig cell differentiation and function.

https://www.pnas.org/content/pnas/95/2/594.full.pdf

Maguelone G. Forest

Papers

Brain processing of visual sexual stimuli in human males

Neuroanatomical correlates of visually evoked sexual arousal in human males.

Hypophyso-gonadal function in humans during the first year of life. 1. Evidence for testicular activity in early infancy

Evidence of testicular activity in early infancy

Receptors for anti-Müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation