scholarly journals Prenatal programming of the female reproductive neuroendocrine system by androgens

Reproduction ◽  
2006 ◽  
Vol 132 (4) ◽  
pp. 539-547 ◽  
Author(s):  
Jane Robinson
Keyword(s):  
Reproductive Function ◽  
Sexually Dimorphic ◽  
Critical Periods ◽  
The Neural Network ◽  
Gnrh Release ◽  
Steroid Sensitive ◽  
Neuroendocrine Axis ◽  
Species Specific ◽  
Male Hormones ◽  
The Brain

It has been clear for several decades that the areas of the brain that control reproductive function are sexually dimorphic and that the ‘programming actions’ of the male gonadal steroids are responsible for sex-specific release of the gonadotrophins from the pituitary gland. The administration of exogenous steroids to fetal/neonatal animals has pinpointed windows of time in an animals’ development when the reproductive neuroendocrine axis is responsive to the organisational influences of androgens. These ‘critical’ periods for sexual differentiation of the brain are trait- and species-specific. The neural network regulating the activity of the gonadotrophin releasing hormone (GnRH) neurones is vital to the control of reproductive function. It appears that early exposure to androgens does not influence the migratory pathway of the GnRH neurone from the olfactory placode or the size of the population of neurones that colonise the postnatal hypothalamus. However, androgens do influence the number and the nature of connections that these neurones make with other neural phenotypes. Gonadal steroid hormones play key roles in the regulation of GnRH release acting largely via steroid-sensitive intermediary neurones that impinge on the GnRH cells. Certain populations of hormonally responsive neurones have been identified that are sexually dimorphic and project from hypothalamic areas known to be involved in the regulation of GnRH release. These neurones are excellent candidates for the programming actions of male hormones in the reproductive neuroendocrine axis of the developing female.

scholarly journals Programming of the reproductive axis by hormonal and genetic manipulation in mice

Reproduction ◽  
2018 ◽  
Author(s):  
Susana B Rulli ◽  
María Julia Cambiasso ◽  
Laura D Ratner
Keyword(s):  
Sex Chromosome ◽  
Genetic Manipulation ◽  
Sex Differentiation ◽  
Reproductive Function ◽  
Gonadal Steroids ◽  
Critical Periods ◽  
Female Reproduction ◽  
Control Male ◽  
Male And Female ◽  
The Brain

In mammals, the reproductive function is controlled by the hypothalamic-pituitary-gonadal axis. During development, mechanisms mediated by gonadal steroids exert an imprinting at the hypothalamic-pituitary level, by establishing sexual differences in the circuits that control male and female reproduction. In rodents, the testicular production of androgens increases drastically during the fetal/neonatal stage. This process is essential for the masculinization of the reproductive tract, genitals and brain. The conversion of androgens to estrogens in the brain is crucial for the male sexual differentiation and behavior. Conversely, feminization of the brain occurs in the absence of high levels of gonadal steroids during the perinatal period in females. Potential genetic contribution to the differentiation of brain cells through direct effects of genes located on sex chromosomes is also relevant. In this review, we will focus on the phenotypic alterations that occur on the hypothalamic-pituitary-gonadal axis of transgenic mice with persistently elevated expression of the human chorionic gonadotropin hormone (hCG). Excess of endogenously synthesized gonadal steroids due to a constant hCG stimulation is able to disrupt the developmental programming of the hypothalamic-pituitary axis in both transgenic males and females. Locally produced estrogens by the hypothalamic aromatase might play a key role in the phenotype of these mice. The “four core genotypes” mouse model demonstrated a potential influence of sex chromosome genes in brain masculinization before critical periods of sex differentiation. Thus, hormonal and genetic factors interact to regulate the local production of the neurosteroids necessary for the programming of the male and female reproductive function.

scholarly journals Identification of KiSS-1 Product Kisspeptin and Steroid-Sensitive Sexually Dimorphic Kisspeptin Neurons in Medaka (Oryzias latipes)

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2467-2476 ◽  
Author(s):  
Shinji Kanda ◽  
Yasuhisa Akazome ◽  
Takuya Matsunaga ◽  
Naoyuki Yamamoto ◽  
Shunji Yamada ◽  
...  
Keyword(s):  
Mammalian Species ◽  
Sexually Dimorphic ◽  
Neuronal System ◽  
Anatomical Distribution ◽  
Neuronal Populations ◽  
Hypothalamic Nuclei ◽  
Steroid Sensitive ◽  
Neuronal Systems ◽  
The Brain

Recently, a novel physiologically active peptide, kisspeptin (metastin), has been reported to facilitate sexual maturation and ovulation by directly stimulating GnRH neurons in several mammalian species. Despite its importance in the neuroendocrine regulation of reproduction, kisspeptin neurons have only been studied in mammals, and there has been no report on the kisspeptin or kisspeptin neuronal systems in nonmammalian vertebrates. We used medaka for the initial identification of the KiSS-1 gene and the anatomical distribution of KiSS-1 mRNA expressing neurons (KiSS-1 neurons) in the brain of nonmammalian species. In situ hybridization for the medaka KiSS-1 gene cloned here proved that two kisspeptin neuronal populations are localized in the hypothalamic nuclei, the nucleus posterioris periventricularis and the nucleus ventral tuberis (NVT). Furthermore, NVT KiSS-1 neurons were sexually dimorphic in number (male neurons ≫ female neurons) under the breeding conditions. We also found that the number of KiSS-1 neurons in the NVT but not that in the nucleus posterioris periventricularis was positively regulated by ovarian estrogens. The fact that there were clear differences in the number of NVT KiSS-1 neurons between the fish under the breeding and nonbreeding conditions strongly suggests that the steroid-sensitive changes in the KiSS-1 mRNA expression in the NVT occur physiologically, according to the changes in the reproductive state. From the present results, we conclude that the medaka KiSS-1 neuronal system is involved in the central regulation of reproductive functions, and, given many experimental advantages, the medaka brain may serve as a good model system to study its physiology.

scholarly journals Overexpression of Glutamic Acid Decarboxylase-67 (GAD-67) in Gonadotropin-Releasing Hormone Neurons Disrupts Migratory Fate and Female Reproductive Function in Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (6) ◽  
pp. 2566-2579 ◽  
Author(s):  
Sabine Heger ◽  
Marianne Seney ◽  
Elizabeth Bless ◽  
Gerald A. Schwarting ◽  
Marie Bilger ◽  
...  
Keyword(s):  
Glutamic Acid Decarboxylase ◽  
Normal Values ◽  
Reproductive Function ◽  
Transgenic Animals ◽  
Mutant Mice ◽  
Acid Decarboxylase ◽  
Gaba Production ◽  
Gnrh Neurons ◽  
Gnrh Release ◽  
The Brain

Abstract γ-Aminobutyric acid (GABA) inhibits the embryonic migration of GnRH neurons and regulates hypothalamic GnRH release. A subset of GnRH neurons expresses GABA along their migratory route in the nasal compartment before entering the brain, suggesting that GABA produced by GnRH neurons may help regulate the migratory process. To examine this hypothesis and the possibility that persistence of GABA production by GnRH neurons may affect subsequent reproductive function, we generated transgenic mice in which the expression of glutamic acid decarboxylase-67 (GAD-67), a key enzyme in GABA synthesis, is targeted to GnRH neurons under the control of the GnRH gene promoter. On embryonic d 15, when GnRH neurons are still migrating, the transgenic animals had more GnRH neurons in aberrant locations in the cerebral cortex and fewer neurons reaching the hypothalamic-preoptic region, whereas migration into the brain was not affected. Hypothalamic GnRH content in mutant mice was low during the first week of postnatal life, increasing to normal values during infantile development (second week after birth) in the presence of increased pulsatile GnRH release. Consistent with these changes, serum LH and FSH levels were also elevated. Gonadotropin release returned to normal values by the time steroid negative feedback became established (fourth week of life). Ovariectomy at this time demonstrated an enhanced gonadotropin response in transgenic animals. Although the onset of puberty, as assessed by the age at vaginal opening and first ovulation, was not affected in the mutant mice, estrous cyclicity and adult reproductive capacity were disrupted. Mutant mice had reduced litter sizes, increased time intervals between deliveries of litters, and a shorter reproductive life span. Thus, GABA produced within GnRH neurons does not delay GnRH neuronal migration, but instead serves as a developmental cue that increases the positional diversity of these neurons within the basal forebrain. In addition, the results suggest that the timely termination of GABA production within the GnRH neuronal network is a prerequisite for normal reproductive function. The possibility arises that similar abnormalities in GABA homeostasis may contribute to syndromes of hypothalamic amenorrhea/oligomenorrhea in humans.

scholarly journals Neurobehavioral effects of choninergic drugs in prenatal period

2017 ◽  
Vol 15 (3) ◽  
pp. 5-21 ◽  
Author(s):  
Elena V. Stashina ◽  
Nikolay A. Gavrilov ◽  
Petr D. Shabanov
Keyword(s):  
Reproductive Function ◽  
Prenatal Development ◽  
Environmental Toxicants ◽  
Critical Periods ◽  
Brain Neurotransmitter ◽  
Neurobehavioral Deficits ◽  
Neurobehavioral Effects ◽  
The Brain ◽  
Prenatal Effects

Environmental toxicants, chemicals exhibiting with cholinotropics properties, and drugs – agonists and antagonists of M- and N-cholinergic receptors by acting on the developing brain of the fetus in the embryonic period of ontogenesis, cause a change the activity of the cholinergic mechanisms of the brain during critical periods of prenatal development with the subsequent disruption of the formation of different brain systems, primarily the ontogeny of nerve cells and brain neurotransmitter systems. These changes in the long term is correlated with neurobehavioral deficits from adult individuals, dysfunction of the reproductive system of adult offspring. The relevance of the study of prenatal effects of cholinergic factors on the central mechanisms of reproductive function, memory processes and learning during ontogenetic development of the organism due to the need of prevention and treatment of subsequent mental, behavioral, and sexual dysfunctions, and abnormal sexual behavior, infertility.

scholarly journals The neuroendocrine timing of puberty

Reproduction ◽  
2005 ◽  
Vol 129 (6) ◽  
pp. 675-683 ◽  
Author(s):  
Francis J P Ebling
Keyword(s):  
Pubertal Development ◽  
Reproductive Function ◽  
Overweight And Obesity ◽  
Neural Systems ◽  
Large Variability ◽  
Somatic Development ◽  
Gnrh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Timing Of Puberty ◽  
Species Specific

Puberty is the attainment of fertility, a process encompassing morphological, physiological and behavioural development. The increased hypothalamic secretion of the gonadotrophin-releasing hormone decapeptide (GnRH) is essential for the activation of the pituitary–gonadal axis at puberty. The GnRH secretory network initially develops and is temporarily active during species-specific periods of fetal/neonatal development, so puberty is the secondary reactivation of an existing system. From a neurobiological perspective, the timing of puberty is therefore a function of changes in the neural systems controlling GnRH release. The large variability between individuals in the onset and progression of puberty indicates that the timing of puberty is not simply a function of chronological age. Rather, the neurotransmitter and neuromodulatory systems that impact upon the GnRH secretory network convey information about metabolic fuels, energy stores and somatic development and, for many species, information about season and social environment. The clear links demonstrated between metabolic fuel availability and reproductive function in many animal models provides evidence that the earlier onset of pubertal development observed in girls in certain US study populations is likely to relate to the increasing prevalence of overweight and obesity in adolescents.

scholarly journals Separate Critical Periods Exist for Testosterone-Induced Differentiation of the Brain and Genitals in Sheep

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2409-2415 ◽  
Author(s):  
Charles E. Roselli ◽  
Charles T. Estill ◽  
Henry L. Stadelman ◽  
Mary Meaker ◽  
Fred Stormshak
Keyword(s):  
Critical Period ◽  
Preoptic Area ◽  
Testosterone Propionate ◽  
Corn Oil ◽  
Normal Female ◽  
Sexually Dimorphic ◽  
Critical Periods ◽  
The Mean ◽  
The Brain ◽  
Sexually Dimorphic Nucleus

Sheep exposed to testosterone during a critical period from gestational day (GD) 30 to GD 90 develop masculine genitals and an enlarged male-typical ovine sexually dimorphic nucleus of the preoptic area (oSDN). The present study tested the hypothesis that separate critical periods exist for masculinization of these two anatomical end points. Pregnant ewes were treated with testosterone propionate (TP) either from GD 30 to GD 60 (early TP) or GD 60 to GD 90 (late TP). Control (C) pregnant ewes were treated with corn oil. Fetuses were delivered at GD 135 and the volume of the oSDN was measured. Early TP females possessed a penis and a scrotum devoid of testes, whereas late TP and C females had normal female genitals. Neither period of TP exposure grossly affected the genitals of male fetuses. Despite masculinized genitals, the mean volume of the oSDN in early TP females (0.32 ± 0.06 mm3) was not different from C females (0.24 ± 0.02 mm3) but was significantly enlarged in late TP females (0.49 ± 0.04 mm3; P < 0.05 vs. C) when the genitals appeared normal. In contrast, the volume of the oSDN in late TP males (0.51 ± 0.02 mm3) was not different from C males (0.51 ± 0.04 mm3) but was significantly smaller in the early TP males (0.35 ± 0.04 mm3; P < 0.05 vs. C). These results demonstrate that the prenatal critical period for androgen-dependent differentiation of the oSDN occurs later than, and can be separated temporally from, the period for development of masculine genitals.

scholarly journals Distinct Mechanisms Involving Diverse Histone Deacetylases Repress Expression of the Two Gonadotropin β-Subunit Genes in Immature Gonadotropes, and Their Actions Are Overcome by Gonadotropin-Releasing Hormone

2007 ◽  
Vol 27 (11) ◽  
pp. 4105-4120 ◽  
Author(s):  
Stefan Lim ◽  
Min Luo ◽  
Mingshi Koh ◽  
Meng Yang ◽  
Mohammed Nizam bin Abdul Kadir ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Reproductive Function ◽  
Gonadotropin Releasing Hormone ◽  
Β Subunit ◽  
Releasing Hormone ◽  
Calcium Calmodulin Dependent ◽  
Gnrh Release ◽  
Dependent Protein ◽  
Reproductive Cycles ◽  
Class Iia Hdacs

ABSTRACT The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced in the embryonic pituitary in response to delivery of the hypothalamic gonadotropin releasing hormone (GnRH). GnRH has a pivotal role in reestablishing gonadotropin levels at puberty in primates, and for many species with extended reproductive cycles, these are reinitiated in response to central nervous system-induced GnRH release. Thus, a clear role is evident for GnRH in overcoming repression of these genes. Although the mechanisms through which GnRH actively stimulates LH and FSH β-subunit (FSHβ) gene transcription have been described in some detail, there is currently no information on how GnRH overcomes repression in order to terminate reproductively inactive stages. We show here that GnRH overcomes histone deacetylase (HDAC)-mediated repression of the gonadotropin β-subunit genes in immature gonadotropes. The repressive factors associated with each of these genes comprise distinct sets of HDACs and corepressors which allow for differentially regulated derepression of these two genes, produced in the same cell by the same regulatory hormone. We find that GnRH activation of calcium/calmodulin-dependent protein kinase I (CaMKI) plays a crucial role in the derepression of the FSHβ gene involving phosphorylation of several class IIa HDACs associated with both the FSHβ and Nur77 genes, and we propose a model for the mechanisms involved. In contrast, derepression of the LH β-subunit gene is not CaMK dependent. This demonstration of HDAC-mediated repression of these genes could explain the temporal shut-down of reproductive function at certain periods of the life cycle, which can easily be reversed by the actions of the hypothalamic regulatory hormone.

scholarly journals Thyroid hormones and seasonal reproductive neuroendocrine interactions

Reproduction ◽  
2008 ◽  
Vol 136 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Nobuhiro Nakao ◽  
Hiroko Ono ◽  
Takashi Yoshimura
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Biological Process ◽  
Critical Role ◽  
Day Length ◽  
Seasonal Reproduction ◽  
Seasonal Breeding ◽  
Length Changes ◽  
Neuroendocrine Axis ◽  
The Brain

Many animals that breed seasonally measure the day length (photoperiod) and use these measurements as predictive information to prepare themselves for annual breeding. For several decades, thyroid hormones have been known to be involved in this biological process; however, their precise roles remain unknown. Recent molecular analyses have revealed that local thyroid hormone activation in the hypothalamus plays a critical role in the regulation of the neuroendocrine axis involved in seasonal reproduction in both birds and mammals. Furthermore, functional genomics analyses have revealed a novel function of the hormone thyrotropin. This hormone plays a key role in signaling day-length changes to the brain and thus triggers seasonal breeding. This review aims to summarize the currently available knowledge on the interactions between elements of the thyroid hormone axis and the neuroendocrine system involved in seasonal reproduction.

scholarly journals The ex-illiterate brain: The critical period, cognitive reserve and HAROLD model

2009 ◽  
Vol 3 (3) ◽  
pp. 222-227 ◽  
Author(s):  
Maria Vania Silva Nunes ◽  
Alexandre Castro-Caldas ◽  
Dolores Del Rio ◽  
Fernado Maestú ◽  
Tomás Ortiz
Keyword(s):  
Recognition Test ◽  
Cognitive Skills ◽  
Critical Period ◽  
Cognitive Reserve ◽  
Brain Activity ◽  
High Educational Level ◽  
Critical Periods ◽  
Language Recognition ◽  
Regular Time ◽  
The Brain

Abstract The lifelong acquisition of cognitive skills shapes the biology of the brain. However, there are critical periods for the best use of the brain to process the acquired information. Objectives: To discuss the critical period of cognitive acquisition, the concept of cognitive reserve and the HAROLD (Hemispheric Asymmetry Reduction in Older adults) model. Methods: Seven women who learned how to read and to write after the age of 50 (ex-illiterates) and five women with 10 years of regular schooling (controls) were submitted to a language recognition test while brain activity was being recorded using magnetoencephalography. Spoken words were delivered binaurally via two plastic tubs terminating in ear inserts, and recordings were made with a whole head magnetometer consisting of 148 magnetometer coils. Results: Both groups performed similarly on the task of identifying target words. Analysis of the number of sources of activity in the left and right hemispheres revealed significant differences between the two groups, showing that ex-illiterate subjects exhibited less brain functional asymmetry during the language task. Conclusions: These results should be interpreted with caution because the groups were small. However, these findings reinforce the concept that poorly educated subjects tend to use the brain for information processing in a different way to subjects with a high educational level or who were schooled at the regular time. Finally, the recruiting of both hemispheres to tackle the language recognition test occurred to a greater degree in the ex-illiterate group where this can be interpreted as a sign of difficulty performing the task.

Sign in / Sign up

Export Citation Format

Share Document