Endocrine modulation of the adolescent brain: a review

Endocrine Modulation of the Adolescent Brain: A Review Carmen T. Molina LicMedT Barbara E. Switzer BA , Hanna Klaus MD 1 Unidad de Reproduccion y Desarrollo, Departamento de Fisiologıa, Facultad de Ciencias Biologicas, Santiago, Pontificia Universidad Catolica de Chile, Chile 2 Fundacion Medica San Cristobal, Santiago, Chile3 Departamento de Ciencias Animales, Facultad de Agronomıa e Ingenierıa Forestal, Pontificia Universidad Catolica de Chile, Santiago, Chile 4 Florida State University College of Medicine, Tallahassee, Florida5 Natural Family Planning Center of Washington, DC, and Teen STAR Program, Bethesda, Maryland, USA Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions andimpulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given thegrowing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, thisarticle reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacityof steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activityto promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomenarelated to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes accountfor most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible fororganizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonicdevelopment and during the transition from puberty to adolescence. This stage becomes a critical organizational window when theappropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent braindevelopment are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucialin the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behaviorclearly evidences a stage of brain development influenced for the most part by steroid hormones.
Key Words: Adolescence, Adolescent behavior, Adolescent brain, Steroid hormones, Neurotransmitters, Psychological disorders Puberty, Adolescence and their Associated Endocrine Changes A series of changes take place during human develop- Adolescent growth and development are influenced by ment; those occurring over adolescence are particularly a series of highly regulated and coordinated endocrine noteworthy. In this stage, a number of physiological vari- changes which start in puberty or shortly before; in fact, the ables promote the manifestation of sexual characteristics, latter is defined as the period in which an individual becomes determining both gender phenotype (male or female) and sexually maturPuberty generally begins at age 8e10 and the capacity for fertility of the individual. The cognitive culminates in menarche at age 12e13 in females.In males, variations experienced in puberty have been widely studied puberty generally begins one year later than in females and in this context over the past years. It has been suggested culminates at completion of spermatogenesis, with the full that, in adolescents, various mental faculties are still development of the spermatogenic During puberty developing. Therefore, they appear exacerbated or dimin- hormonal changes culminate in expulsion of mature oocytes ished in youngsters as compared to adults. The purpose of from the ovaryand of mature spermatozoa from the testes.
the present review is to offer evidence of the effects on Recently, numerous studies have focused on this topic; brain development exerted by gonadal steroid hormones, however, the endocrine mechanisms underlying the onset of which increase during adolescence. Hence, this stage can be puberty remain to be elucidated. It is known that one of the understood as a unique opportunity in which the changes main hormonal signals linked to puberty corresponds to an taking place in the encephalon might determine character increase in the levels of leptin, a protein hormone thought to as well as certain behavior patterns in later stages such as be one of the key signalling agents involved in triggering puberty. Leptin is a fundamental regulator of lipid homeo-stasis and, therefore, of adiposity. Thus, an increase in leptinis related to the rise in adiposity associated with puberty The authors do not have any potential conflicts of interest to disclose associated While the hormonal mechanisms triggering puberty have * Address correspondence to: Pilar Vigil, MD, PhD, Unidad de Reproduccion y not been fully described yet, it is certain that one of the Desarrollo, Departamento de Fisiologıa, Facultad de Ciencias Biologicas, Pontificia events signalling the onset of puberty is the activation of the olica de Chile. Av. Alameda B. O’Higgins 340, Santiago, Chile hypothalamic-hypophyseal-gonadal As a component 1083-3188/$ - see front matter Ó 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc.
doi: P. Vigil et al. / J Pediatr Adolesc Gynecol 24 (2011) 330e337 of this axis, the hypothalamus starts releasing pulses of correctly. Coupled with this egocentrism there is consider- gonadotropin-releasing hormone, which exerts its stimu- able excitability, which leads to emotionally basing their lating effect on the hypophysis. This stimulation causes the decision-making. These aspects are signs of developing cognitive maturity, a process which is seldom smooth.
hormone and the luteinizing hormone, which exert their Behaviors can originate from outside the person (exog- multiple functions on the gonads increasing biosynthesis enously) or within the person (endogenously). Exogenous and secretion of steroid hormones, mainly estrogens, behavior is generated by external stimuli, such as sensory progesterone, and testost; this is considered another perceptions or emotional responses to perceived situations biological marker for puberty. The increased hormonal levels which may or may not be factual. Contrary to a reflex act cause the expression of secondary sexual characteristics, e.g., produced by the stimulation of the spinal cord, exogenous breast development in women and facial hair in Most behavior involves the immediate participation of brain probably the levels of several other hormones also vary at the regions in response to external stimuli, generating sponta- onset or throughout puberty, among them an increase in neous behavior. On the other hand, endogenous behavior is growth Recent reports have also found fluctua- triggered by cognitive control involving antecedent goal- tions in the levels of insulin, insulin-like growth factor 1, directed planning behavior. Endogenous behavior requires kisspeptinand ghramong others, but further the participation of a higher number of brain research is needed in order to understand their role at the and is a behavior acquired in the early stages of the indi- beginning and progression of puberty.
vidual’s development. It continues to develop during On the other hand, adolescence —from the Latin ado- adolescence and probably throughout life. Lunastates lescere, meaning “to grow into maturity”— is the period of that adolescents can be expected to present predominantly transition from childhood to adulthood, and involves exogenous behavior since their endogenous behavior is still a number of changes in the psychological, social, and physiological development of a particular individual, Each stage of development is characterized by possess- including capacity for mature sexual behavior.The ing a certain speed for processing sensory information. This physical changes associated with puberty begin as early as processing speed begins to decrease in infancy and during 7 or 8 years of age and are generally completed by age adolescence, until it reaches adult levels.Both exoge- 16e18, while the psychological changes associated with nous and endogenous behaviors require a precise process- adolescence occur between the ages of 12 and 21. The ing speed to guarantee the correct emission of responses.
modulation of the limbic-cortical circuits which leads to the The optimal speed for processing information is reached acquisition of adult cognition and the establishment of during adolescence leading to an adequate balance between information pathways to promote social development in endogenous and exogenous behaviorsfor this reason the individual is characteristic of adolescence.
some cognitive/logic tasks appear to be specially difficultduring this stage of adjustment.
Some Considerations on Adolescent Behavior Another characteristic of adolescent behavior is impulse control. Impulsive behavior interferes with the execution of The transition from puberty to adolescence is a complex behavior aimed at reaching a certain goal, e.g., good school period from the perspective of the individual; during performance. In order to acquire this capacity, the indi- adolescence youngsters evidence a wide variety of vidual needs to be able to regulate his impulsive and irra- behavioral patterns that often disappear in adulthood.
tional behavior by selectively blocking the generated The rapid succession of changes in their psychic and phys- responses.This process involves discriminating the ical development is often confusing to teens, leading to information received. During adolescence, youngsters erratic behavior. Youngsters often make irrational decisions appear to be unable to perform this selective inhibition; this inability inclines teens toward behaviors which yield substances, participating in extreme sports or adventures, immediate gratification even if risky, but which appear to and early—sometimes promiscuous—sexual activity, with be more attractive than those activities with long-term the subsequent danger of sexually transmitted diseases and unplanned pregnancies. In this period, individuals are easily In brief, during adolescence there is an incomplete overcome by stressful situations and show great difficulty in development of the encephalic functions that determine performing tasks that demand inhibition of impulsive endogenous (voluntary) behavior. In addition, there is an exacerbated influence of immediate or short-term incen- Adolescents are also characterized by egocentrism. This tives. This generates limitations to discriminate information has been defined as the inability to differentiate boundaries errors, to maintain a voluntary state of control, and to feel in subject-object interactions; others are viewed as an motivation towards a future reward. This set of processes is extension of oneself. has suggested that during still developing, which explains the greater part of typical adolescence in particular, youngsters’ egocentrism is char- acterized by the belief that they are special and unique, andthat others are excessively focused on their appearance and behaviorEgocentrism is distinguished both by a lack of‘common sense’ in decision making and rigidity in Neurological development in adolescence is associated reasoning, related to being unable to integrate information to the acquisition of cognitive control and affective P. Vigil et al. / J Pediatr Adolesc Gynecol 24 (2011) 330e337 modulation. It has been by functional magnetic nervous system. Binding to its membrane receptors triggers resonance imaging, that the encephalic regions normally the opening of the associated chloride channel. When this activated in an adolescent during elaboration of an answer anion enters the neuron, chloride produces hyperpolariza- differ from those used in an adult, who would require fewer tion, preventing synaptic transmission of nervous impulses.
regions to elaborate the same answer. Therefore, it is This way, the GABAergic system can be used as an “inter- possible to suggest a suboptimal use of the brain on the part rupting mechanism” to control the excitability of the of teenagers.Moreover, sleep deprivation, so common in nervous syThus, an increase in GABAergic activity this period, has been shown to aggravate this situation by would reduce excitation of the individual, whereas an inhi- altering the normal activation of certain brain regions. This bition of such activity would produce increased neural affects information processing, leads to behavioral modifi- excitement (and probably anxiety) in the individual. Shen cation, and generates a number of emotional problems.
et have described replacement of the a1 subunit of the During adolescence, the connections that determine GABA receptor by its homologous a4 during endogenous behavior are still immature. It has been sug- the latter possesses an arginine residue which causes gested that humans may possess a "motivational circuit,” a decrease in chloride intake altering normal inhibition in where the limbic-cortical routes interact. In this circuit, the the nervous system. This particular function of the cortical system would act as a filter to the stimuli sent by the GABAergic system in adolescence may be responsible for the limbic system, inhibiting the stimuli that lead to risky or excitement phenomena observed due to the action of 17- inconvenient actions, and consciously responding to any hydroxyprogesterone (17OHP, a hormone (neurosteroid) stimuli favorable to the individual and his immediate that acts by binding GABA receptors) during this stage of life, environment. During late adolescence, the connections as opposed to the inhibitory episodes caused by the same which regulate this circuit mature.This route, immature compound in adult life.According to some authors,this in adolescents, is based on the "selection" on the part of the role is especially relevant in this period for development of cortical system of the motivational behaviors generated by the audacious behaviors necessary in this stage. Thus the the limbic system. This circuit contains a neuron population thoughtlessness involved in adolescent decision making with a defined activation pattern which is part of the could be seen as a survival mechanism necessary for species connection pathways between the prefrontal and the adapFor example, many young individuals need to ventral striate cortex, then the thalamus, and finally back to risk their lives to learn to hunt for survival. In some adults “excitatory adolescent GABA receptors” may continue to The links in the motivation circuit develop during bind 17OHP as in adolescence. In these cases, 17OHP would adolescence; in this period, the limbic-cortical systems are continue to exert an excitatory response instead of the weakly connected, presenting limited cross-communication inhibitory response expected to be present in adult life. This regarding the adequate selection of motivational behaviors.
could explain the anxiety and depression which some Impulsivity decreases throughout childhood and adoles- women experience at certain stages of the menstrual cycle cence, secondary to maturation of the prefrontal corte and upon ingestion of steroid hormones for hormone At the same time, the regions linked to emotional behavior, replacement therapy or contracebecause the 17 OHP generation of feelings, and affective information (nucleus would bind to this form of “excitatory adolescent” GABA receptor still present in adulthood. Thus teenage behavior compared to the same regions of children and adults.Even can be partially explained by processes of neural connec- though both the cortical regions and the limbic system are tivity, but the explanation must also include differences at still under development, it has been suggested that in this the molecular signalling level which determine the post- stage the activation of the limbic system exceeds that of the synaptic regulatory responses of the central nervous system.
cortical systems, leading to the predominance of theemotional component of behavior.Towards the end ofadolescence, neural activity in both systems reaches similar Current Evidence of the Effects Exerted by Gonadal Steroid values, affording the balance needed to issue adequate integrated responses to the stimuli elicited by the limbic-cortical system.Thus the systems that control the Steroid hormones such as estrogens, progesterone, and prefrontal cortex are required to inhibit inappropriate testosterone exert a role on the central nervous system, as responses, favouring the execution of planned behavior.
has been described for 17OHP. Some studieshave made The previously described conditions lead us to conclude it possible to classify the effects of these hormones as that adolescent behavior is the result of a set of neural organizational or activational. Activational effects of sex connections that are still being established, determining steroids modify neural activity to favor a certain conduct a series of behavioral differences that will be acquired at the in a specific contextActivational effects are not beginning of adult life. In addition to these variations in permanent, but appear only in the presence of the neural connection networks, there are molecular events hormone. Organizational effects, in turn, are related to the occurring in this stage which may also explain some patterns capacity of sex steroids to determine the structure of of conduct in teenagers. One of the main differences found in the nervous system during its development. These effects people this age is related to the molecular mechanism of are permanent, remain after exposure to the steroid, and action of gamma-aminobutyric acid (GABA). GABA consti- allow for the generation of activational responses to tutes the main inhibitory neurotransmitter of the central P. Vigil et al. / J Pediatr Adolesc Gynecol 24 (2011) 330e337 During embryonic development the nervous system is language and communication skills; as well as the corpus highly sensitive to gonadal steroid hormones. It is in this stage that organizational modifications occurHowever, it formation of memory; the locus coeruleuswhich is has been observed that a series of important processes related to panic and stress behavior; and the periventricular involving organizational development of the nervous anteroventral nucleus,which is associated with feedback system also occur during During this period, regulation of gonadotrophic hormone secretion. At the sex steroids produce a structural remodelling of the circuits same time, the male brain has other areas of comparatively that determine the behavioral response to hormonal or greater volume than the female brain such as: the inferior sensory stimuli in For this reason, adolescence parietal lobule, an area of integration of sensory-motor represents a second stage of development of the nervous the visual cortex, in charge of processing system in which the gonadal hormones secreted during the visual information from the the amygdala, puberty exert a series of organizational changes.
linked to the processing of emotions;the stria terminalis,which participates in the integration of the amygdala to cortical regioand the sexually dimorphic nucleus ofthe preoptic area, involved in sexual behavior The brain is an organ which presents sexual dimor- The sexual dimorphism of the brain and the endocrine phism; its morphology varies depending on the sex of the differences between males and females may explain the individual.Over the past three decades, our under- differential prevalence of mood disorders in sex and gender standing of the characterization of mammalian brain of the individuals. It is known that certain mood and structures as related to being male or female, man or anxiety disorders are more frequent among woThis woman, has increased considerably. These advances have could be explained on the basis of the hormonal and subsequently led to a deeper knowledge about the role of organizational characteristics of women.
steroid hormones in the development of the humanbeing. In mammals, brain sexual dimorphism appears during exposure to different concentrations of gonadalsteroid hormones.In males, the level of androgens such as testosterone present in perinatal life organizes thenuclei of the limbic and hypothalamic systems as well as Far from being considered a rigid system, the brain is that of the dorsal cord, influencing a given behavior in currently understood as a dynamic structure with neural later stages of life. Thus if androgen levels are below those networks which frequently interact and are able to modify considered to be normal for the species at this stage of themselves, generating great structural and functional development, formation of different nuclei will be altered, complexity. One of the most frequently studied changes as is the case with the corpus callosum which connects affecting the brain relates to the variation in white and gray the cortical hemispheres and facilitates the rapid transfer matter. Through the use of magnetic resonance images, it of information between cortical areasRather than has been possible to establish that there is a linear increase being one homogeneous bundle of fibers, subsections of of white matter and a net reduction of gray matter during the corpus callosum vary dramatically in quantitative In fact, several periods have been identified characteristics of axon density, size, and degree of mye- in which the encephalon is more susceptible to undergo linatiIn the male macaque and the rat, corpus cal- both organizational and activational changes. During losum also is larger than in females due to a higher a normal individual’s life, his brain will present great neural density of axons (around 10 million more).Some plasticity during the embryonic period and puberty. The authormaintain that during embryonic development, organizational changes which occur in the brain during exposure to fetal testosterone during critical periods of adolescence are based on four functional mechanisms, fetal brain development slows the maturation of the left myelination, neural pruning, apoptosis, and dendritic spine hemisphere, thus allowing the right hemisphere to ach- ieve dominance. The delayed development of left hemi-sphere functions in males may explain many of the observed trends: accelerated language development in Myelination is the process by which axons are covered by females, males’ enhanced performance of visuospatial myelin sheaths; myelin is mainly lipid, allowing for the tasks, and their higher incidence of left-handedness. The saltatory conduction of the nerve impulse which gives the organizational effects caused by steroid hormones cause system a higher transmission speed. In the central nervous variations in the volume of certain brain regions, the system, myelin is supplied by the oligodendrocytes; number and density of neurones, the extent and ramifi- whereas in the peripheral nervous system, this electric cation of synaptic connections, among others.
insulator is provided by Schwann cells. In the central Sexual dimorphism is not only determined during the nervous system this process can be influenced by the action perinatal period. Several recent studies have shown that of gonadal steroid hormones.Both estradiol and proges- some of these differences may have their origin or even terone facilitate myelination in the female, inducing synthesis of the basic myelin protein in oligodendrocytes, brain presents a proportionally higher volume in regions while in the male testosterone is crucial to the process of such as Broca’s and Wernicke’s associated with myelination, partly because administration of testosterone P. Vigil et al. / J Pediatr Adolesc Gynecol 24 (2011) 330e337 to oligodendrocytes induces their maturity and myelin Schulz’s shows that copulatory behavior in adult rodents requires the presence of testosterone both inpuberty and in adult life. Therefore, the copulatory sexual response corresponds to an activational hormonal effect.
During development, both the number of neurons and However, this behavior can only occur through a prior the number of connections among them vary. Synaptic organizational change triggered by exposure to testosterone density (i.e., number of synapses per unit of brain tissue during puberty which coordinates the neural circuits volume) increases during the early development of an needed to effect sexual behavior in the presence of steroid individual, known as synaptogenesis; there is a subsequent hormones and a female individual. It can be claimed that these organizational events did not occur during prenatal in which the most frequently used connections development because those hamsters did not present such are strengthened and preserved, while synapses which sexual behavior in the same circumstances in the prepu- have shown scarce activation degenerate. Thus the system bertal period.The copulatory sexual behavior was only acquires a more efficient synaptic configuration as only the present in adults who, in their pubertal period, had func- regions directly involved in responding to a given task are tional gonads capable of secreting physiological amounts of steroid hormones. For this reason, prepubertal gonadec-tomy abolished an adult rodent’s copulatory behavior; while postpubertal gonadectomy had no effect on the Programmed cell death affects neurons. Apoptosis allows subjects after administration of testosterone.
for variation of both the volume of different brain areas and Sexual behavior is evident only in adult rodents who the number of available neurons, and is also considered have been subjected to physiological concentrations of a mechanism of the neural plasticity which operated mainly steroid hormones during puberty. Based on this evidence, during embryonic development. Estradiol presents a dual one can suggest that certain organizational processes take mechanism as regards apoptosis, acting as an anti-apoptotic place during adolescence. Scores on a spatial ability agent capable of promoting cell division and cell prolifera- were higher in control (normal) human subjects than in tion in brain cortical neurons in rats,and as a pro- subjects with prepubertal idiopathic hypogonadism and apoptotic agent, triggering a decrease in the volume of the administration after puberty did not affect the scoresobtained by the subjects in either of the hypogonadic Neural dendrites are covered by small extensions called groups.These results suggest that the organizational dendritic spines, which correspond to the anatomical site changes which determine the development of spatial abil- where synapses occur.These structures are dynamic and ities in an individual are also activated during adolescence can grow, persist, or degenerate; hence each dendrite and that physiological levels of testosterone produced by presents different spinal remodelling. Exogenous elements functioning gonads are required. As in the example of the i.e., pathologies, aging, and gonadal steroid hormones can copulatory behavior in hamsters, the absence of effect on alter remodelling.In mammals, the number of dendritic the acquisition of spatial abilities due to testosterone spines changes over the course of the female hormonal administration during the postpubertal period implies the cycle; neurons present a higher density of synaptic spines in existence of a defined period for the occurrence of these proestrus than in estrus and diestrus.
According to these data adolescence can be viewed as a window of opportunity when structural (organizational) Brain organizational modifications were first thought to modifications necessary for the acquisition of certain acti- occur only during embryonic development, whereas only vational effects occur. This window of opportunity is time (hormonally mediated) activational effects took place during puberty. However, recent have sug- hormones which cannot be exerted except within this gested that both activational and organizational changes interval. Hence, it is possible to suggest that puberty is a critical period when diverse modifications which affect Among current experimental models, one of the most the encephalon determine the adult individual’s behavior.
representative is based on a reproductive behavioral study Regardless of the mechanism of brain organization, the in rodents, in which male hamster copulatory behavior in effect exerted by steroid hormones on this process is due to the presence of female hamsters was assessed. This pattern the interaction of these molecules with the neural receptors is commonly observed among adult individuals and is evi- and, later, to the coordination and subsequent execution of denced in copulation. In this experiment, prepubertal a certain cell response. A better understanding of these subjects who had received testosterone did not copulate.
phenomena can be approached through the study of Similarly, adult male hamsters who had been castrated in intracellular signalling pathways used by steroid hormones the prepubertal period, and who had been given testos- in other cell types. Over the last years it has been proposed terone, also failed to copulate in the presence of female that steroidal hormones possess two signalling pathway hamsters. But administration of testosterone to male adult components: the genomic effects and the non-genomic hamsters castrated during the postpubertal period imme- effects. The former correspond to the classic mechanism diately generated copulatory responses.
of action of these hormones, according to which there are P. Vigil et al. / J Pediatr Adolesc Gynecol 24 (2011) 330e337 cytoplasmic receptors capable of interacting with them, also exerting a role in the development of the nervous dimerizing, translocating to the nucleus, and transcribing system through the neural plasticity mechanisms previ- the required gThe non-genomic effects are ously described. One of the main milestones of adolescence generated by the interaction of steroidal hormones and is the organizational development of the brain by the sex membrane receptors, which act through the classical hormones secreted in puberty. Taking into consideration second messengers such as Ca2þ, phosphatidylinositol tri- the above, puberty and adolescence are closely linked in sphosphate, and diacylglycerol, among Non- considering the brain as a target organ which responds to genomic effects can be observed within minutes, whereas genomic effects take hours to develop.
Currently, further analysis is needed as regards the study Psychological Alterations Associated with Endocrine Disorders of the effects of steroidal hormones before being able todetermine whether the observed effects are genomic or Current knowledge regarding the effects of gonadal non-genomic. For this type of approach, the spermatozoon steroid hormones on behavior is limited; however, the constitutes a model of study.During development this presence of endocrine disorders and their connection with cell loses its ability to transcribe genes; therefore, only the behavior point to some link between them. Over the pre- non-genomic signalling pathways are available to the and postnatal period, the organizational effects taking place in the brain will help determine the behavior of the indi- Another advantage presented by this model of non- vidual in his adult life.Similarly, during adolescence genomic pathways is that mammalian spermatozoa and steroid hormones modify both the structure of the nervous neurons are strikingly similar as far as their receptors are connections and the number of neurotransmitter receptors involved,suggesting that both types of cell possess present in the neurons. These changes could exert a role in a comparable ability to react to the same hormonal changes the ability of the nervous system to respond to endogenous in the milieu. It has been recently proposed that steroid or exogenous variables, leading to mood and affective disorders.This concept is supported by studies which would act at the cellular level in the spermatozoon regu- show that free testosterone (the bioactive form of this lating the occurrence of the acrosome reaction hormone) is related to premenstrual syndrome and a modification that is necessary so that it can go through the zona pellucida, penetrate the oocyte and fuse with it, An example of a pathology that may be associated to constituting a crucial event for reproduction.It has been psychological alterations is polycystic ovary syndrome observed that the responses of spermatozoa and neurons to (PCOS), an endocrine disorder defined as an ovulatory the interactions between steroid hormones and the dysfunction caused by hyperandrogenism and/or hyper- GABAergic system are similarIn the light of this evidence, androgenemia and which can frequently be linked to it seems reasonable to think that the changes in the levels of metabolic diseases such as insulin It is diag- sex steroids play a part in puberty, influencing not only nosed mainly among fertile women, with a prevalence of the reproductive system, but also having a certain impact on 5e10 %.Even though this pathology is considered to be brain development and organization taking place in characteristic of the reproductive age, some of its manifes- this period. According to this hypothesis, puberty and tations have been known to appear in early stages of life, adolescence are intrinsically linked in so far as the brain and even in the intra-uterine period.Women suffering constitutes a target for steroid hormones. GABA, a neuro- from PCOS show a high correlation between their abnormal transmitter generally associated to inhibitory action in the androgen levels and the incidence of mood disorders, central nervous system, and progesterone, a neuroactive ranging from affective problems to alterations in sexual steroid, would influence mood swings in women under- identity and depression.A Rorschach study on PCOS going hormonal replacement therapybesides, both subjectsshowed that PCOS women evidenced distortions induce AR in human spermatozoa.Progesterone and in the configuration of the physical and psychological self: GABA would act in a similar way, both in neurons (negative the women tend to think they are at a disadvantage mood) and in spermatozoa (AR inductor). Estradiol, in compared to others, and tend to be hypercritical of them- turn, presents the opposite effect to those of progesterone selves and intolerant of factors outside the norm.These and GABA, both in the nervous system and in spermatozoa, characteristics could result from their hormonal imbalance.
since it causes a state of euthymia and inhibits AR in Although steroid hormones exert some degree of control on mood, they also are capable of predisposing to certain On the basis of the aforementioned data one may psycho-affective disorders. The appearance of such prob- propose that, in certain cases, steroid hormones and the lems may be related both to the organizational effects GABAergic system would interact in analogous ways, both produced in the perinatal period and adolescence and to in spermatozoa and in neurons. Future research could use activational effects produced by the steroids secreted the spermatozoon as a model to understand the non- genomic effects involved in the molecular interaction The incidence of exogenous factors in this brain/ hormone dynamic could affect the organizational processes The increase of steroid hormones during puberty is which take place in adolescence. Sleep deprivation together linked to the individual’s development of secondary sexual with consumption of nicotine, alcohol, steroid hormones, characteristics. However, during adolescence hormones are and various types of drugs during adolescence may P. Vigil et al. / J Pediatr Adolesc Gynecol 24 (2011) 330e337 generate alterations in brain organization, and could 11. Roa J, Garcıa-Galiano D, Castellano JM, et al: Metabolic control of puberty onset: new players, new mechanisms. Mol Cell Endocrinol 2010; 324:87 manifest themselves as behavioral and psycho-affective 12. Lerner R, Steinberg L: Handbook of Adolescent Psychology. New York, Wiley, 13. Piaget J: Comments on Vygotsky’s critical remarks concerning “The language and thought of the child” and “Judgment and reasoning in the child”.
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