RESUMO
Using histomorphological and functional criteria we describe the feedback mechanisms which could play a role in the regulation of the gonadotrophic axis during the postnatal transition to puberty in male lambs. The working hypothesis was that the testicular factors change the peripheral levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by influencing the synthesis rate and storage of LH and FSH in adenohypophyseal gonadotroph cells of weanling and weaned pubertal lambs. The examination was made in (i) 9-week-old infantiles, suckling lambs undergoing weaning, testis-intact (TEI) and orchidectomised (ORCHX) at the 6th week of age, and (ii) 16-week-old pubertal lambs TEI and ORCHX at the 12th week of age (n=5 per group). Changes in gonadotrophs were assayed with hybridohistochemistry, immunohistochemistry and radioimmunoassay. The percentage of the adenohypophyseal area (PA) occupied by cells containing LHß-mRNA and FSHß-mRNA and peripheral levels of both gonadotrophins were lower (P<0.01) in the 16-week-old TEI lambs in comparison with the 9-week-old ones. The PA occupied by cells immunoreactive for LHß was lower (P<0.01), whereas in the case of FSH was greater (P<0.001) in the 16-week-old lambs. After orchidectomy the PA occupied by gonadotrophs stained for LHß-mRNA was greater (P<0.01) in 16-week-old lambs. The PA occupied by LHß-labelled cells was lower (P<0.05) in the 9-week-old ORCHX lambs, whereas in 16-week-old ones was higher (P<0.05) in comparison with the TEI lambs. The circulating LH was greater (P<0.01) in the ORCHX 9- and 16-week-old lambs compared to the TEI ones. The PA occupied by cells containing FSHß-mRNA and the plasma FSH concentration were greater (P<0.001) after orchidectomy in lambs from both age stages. The PA occupied by FSHß-labelled cells was greater (P<0.01) in the 9-week-old ORCHX lambs, whereas in 16-week-old ones was lower (P<0.05) compared to the lambs from TEI groups. In conclusion, in infantile lambs testicular factors may play inhibitory role in regulating FSH synthesis rate, storage and release in contrast to the stimulatory role in regulating LH storage reflected by the inhibitory role in regulating LH release. In lambs at the beginning of puberty, testicular factors may play inhibitory role in regulating LH synthesis rate, storage and release in contrast to the stimulatory role in regulating FSH storage reflected by the inhibitory role in regulating FSH synthesis rate and release. The effects of testicular hormones on the gonadotrophin storage, i.e. releasable pools in adenohypophyseal cells, are specific for both LH and FSH in lambs during the postnatal transition to puberty. Thus, the initiation of puberty in male sheep is a function of change of the inhibitory role of gonadal factors in regulating FSH storage to the stimulatory one and the stimulatory role of gonadal factors in regulating LH storage to the inhibitory one.
Assuntos
Hormônio Foliculoestimulante/metabolismo , Gonadotrofos/metabolismo , Hormônio Luteinizante/metabolismo , Maturidade Sexual/fisiologia , Ovinos/fisiologia , Hormônios Testiculares/fisiologia , Envelhecimento , Animais , Hormônio Foliculoestimulante/análise , Hormônio Foliculoestimulante/sangue , Subunidade beta do Hormônio Folículoestimulante/genética , Gonadotrofos/química , Histocitoquímica , Hormônio Luteinizante/análise , Hormônio Luteinizante/sangue , Hormônio Luteinizante Subunidade beta/genética , Masculino , Orquiectomia , RNA Mensageiro/análise , Testosterona/sangueRESUMO
A fully developed, functional epididymis is important for male fertility. In particular, it is apparent that without the most proximal region, the initial segment (IS), infertility results. Therefore, it is important to understand the development and regulation of this crucial epididymal region. We have previously shown that many functions of the IS are regulated by luminal fluid factors/lumicrine factors from the testis. This study provides evidence that lumicrine factors activated the ERK pathway only in epithelial cells of the IS from Postnatal Day (P) 14 to P19 and sustained this activation into adulthood. The activated ERK pathway promoted cell proliferation and differentiation in the developing IS, although in the adult, its role was switched to maintain cell survival. To understand further the regulation of cell proliferation in the IS, we examined the role of DUSP6, an MAPK1/3 (ERK1/2) preferred phosphatase that is also regulated by lumicrine factors in the IS. Utilizing Dusp6(-/-) mice, our studies, surprisingly, revealed that Dusp6 was a major regulator of cell proliferation in the caput and corpus regions, whereas components of the ERK pathway, together with PTEN and SRC, were the major regulators of cell proliferation in the IS. We hypothesize that region-specific regulation of cell proliferation is caused by differences in the balance of activities between pro- and antiproliferation signaling pathway components for each epididymal region. An understanding of the mechanisms of cell proliferation may provide clues as to why the epididymis rarely succumbs to cancer.
Assuntos
Proliferação de Células , Fosfatase 6 de Especificidade Dupla/fisiologia , Epididimo/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Envelhecimento , Animais , Sobrevivência Celular , Fosfatase 6 de Especificidade Dupla/genética , Epididimo/citologia , Epididimo/crescimento & desenvolvimento , Epididimo/cirurgia , Regulação da Expressão Gênica no Desenvolvimento , Genes src/fisiologia , Ligadura , Masculino , Camundongos , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/genética , Especificidade de Órgãos , PTEN Fosfo-Hidrolase/fisiologia , Fosforilação , Análise Serial de Proteínas , RNA Mensageiro/metabolismo , Hormônios Testiculares/fisiologiaRESUMO
The hypothalamic-pituitary-gonadal (HPG) axis is involved in both the regulation of growth of the developing testis and in controlling spermatogenic and steroidogenic activity in the adult testis. Here, we develop a novel testicular xenografting model to examine to which degree testicular growth and function are controlled by intra- and extratesticular factors. Two or eight halves of neonatal Djungarian hamster testes were implanted into intact, hemicastrated, or castrated nude mouse recipients, and the development of the grafts under reduced or increased competition of testicular tissue was monitored and analyzed. We hypothesized that the outgrowth of the testicular grafts is influenced by the total amount of testicular tissue present in a host and that less testicular tissue in a host would result in more extended outgrowth of the grafts. Our results reveal that the hypothesis is wrong, because implanted hamster testis tissue irrespectively of the grafting condition grows to a similar size revealing an intrinsic mechanism for testicular growth. In contrast, similar size of seminal vesicle as bio-indicator of androgen levels in all hosts revealed that the steroidogenic activity is independent from the mass of testicular tissue and that steroid levels are extrinsically regulated by the recipient's HPG axis. We propose that the model of testicular xenografting provides highly valuable options to explore testicular growth and endocrine regulation of the HPG axis.
Assuntos
Modelos Teóricos , Hormônios Testiculares/fisiologia , Testículo/anatomia & histologia , Testículo/crescimento & desenvolvimento , Testículo/transplante , Animais , Animais Recém-Nascidos , Peso Corporal , Células Cultivadas , Cricetinae , Sistema Endócrino/fisiologia , Masculino , Camundongos , Camundongos Nus , Orquiectomia , Tamanho do Órgão/fisiologia , Phodopus , Hormônios Testiculares/metabolismo , Testículo/fisiologia , Transplante HeterólogoRESUMO
Anti-mullerian hormone, also called AMH, belongs to the large family of transforming growth factor P. Its role in the sexual differentiation of male fetus is now well known. Recently, AMH has been demonstrated to play an important role in the ovarian function. In fact, AMH seems to regulate the kinetics of follicular development, inhibiting the follicular recruitment and the follicular growth. Thus, this intra-gonadic cybernin could be a decisive determinant of the rapidity of follicular pool exhaustion. Today, some experimental data from the literature suggest that AMH could be a reliable marker of ovarian reserve. This review summarizes the present knowledge about AMH and its role in physiology but also in ovarian pathology.
Assuntos
Glicoproteínas/fisiologia , Ovário/fisiologia , Hormônios Testiculares/fisiologia , Hormônio Antimülleriano , Biomarcadores/análise , Feminino , Glicoproteínas/análise , Hormônios Esteroides Gonadais/fisiologia , Humanos , Ductos Paramesonéfricos/fisiologia , Neuropeptídeos/fisiologia , Doenças Ovarianas/diagnóstico , Folículo Ovariano/fisiologia , Hormônios Testiculares/análise , Fator de Crescimento Transformador beta/fisiologiaRESUMO
OBJECTIVE: To examine Mullerian Inhibiting Substance (MIS) as an emerging diagnostic marker of ovarian function. DESIGN: Medline review of published studies pertaining to the role of MIS in assessing ovarian aging, predicting response to ovulation induction in preparation for in vitro fertilization, assessing risk of developing ovarian hyperstimulation (OHSS) before ovulation induction, and diagnosis of polycystic ovarian disease (PCOS). RESULT(S): The majority of published studies to date support a role for MIS as a marker of ovarian reserve. Specific cut-off values are dependent upon the particular assay used. Mullerian Inhibiting Substance may offer value in assessing risk of OHSS and diagnosis of PCOS. CONCLUSION(S): Potential advantages of MIS compared with other conventional markers of ovarian reserve include: 1) MIS is the earliest marker to change with age; 2) it has the least intercycle variability; 3) it has the least intracycle variability; and 4) it may be informative if randomly obtained during the cycle. Widespread clinical use of MIS may await the availability of an international standard for MIS so that results using different assays may be reliably compared.
Assuntos
Glicoproteínas/fisiologia , Ovário/crescimento & desenvolvimento , Hormônios Testiculares/fisiologia , Hormônio Antimülleriano , Feminino , Tumor de Células da Granulosa/diagnóstico , Humanos , Ciclo Menstrual , Síndrome de Hiperestimulação Ovariana/fisiopatologia , Neoplasias Ovarianas/diagnóstico , Indução da Ovulação , Síndrome do Ovário Policístico/fisiopatologiaRESUMO
The Anti-Mullerian hormone (AMH), which is produced by fetal Sertoli cells, is responsible for regression of Mullerian ducts, the anlagen for uterus and Fallopian tubes, during male sex differentiation. Ovarian granulosa cells also secrete AMH from late in fetal life. The patterns of expression of AMH and its type II receptor in the post-natal ovary indicate that AMH may play an important role in ovarian folliculogenesis. Recent advances in the physiological role of AMH has stimulated interest in the significance of AMH as a diagnostic marker and therapeutic agent for ovarian cancer. Currently, AMH has been shown to be a circulating marker specifically for granulosa cell tumour (GCT). Its diagnostic performance seems to be very good, with a sensitivity ranging between 76 and 93%. In patients treated for GCT, AMH may be used post-operatively as marker for the efficacy of surgery and for disease recurrence. Based on the physiological inhibitory role of AMH in the Mullerian ducts, it has been proposed that AMH may inhibit epithelial ovarian cancer cell both in vitro and in vivo. These observations will be the basis for future research aiming to investigate the possible clinical role of AMH as neo-adjuvant, or most probably adjuvant, therapy for ovarian cancer.
Assuntos
Antineoplásicos/uso terapêutico , Glicoproteínas/fisiologia , Glicoproteínas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/fisiopatologia , Hormônios Testiculares/fisiologia , Hormônios Testiculares/uso terapêutico , Hormônio Antimülleriano , Biomarcadores Tumorais/sangue , Feminino , Glicoproteínas/sangue , Humanos , Neoplasias Ovarianas/patologia , Hormônios Testiculares/sangueRESUMO
Anti-Müllerian Hormone (AMH) is a member of the transforming Growth Factor-B (TGF-B) family synthesized exclusively by the gonads of both sexes. Over the last four years, numerous studies have examined the clinical usefulness of serum AMH levels as a predictor of ovarian response and pregnancy in assisted reproductive technology cycles. Assessment of ovarian reserve in women undergoing assisted reproduction is useful in optimising the treatment protocol. Availability of a reliable measure of ovarian reserve is essential. Currently, serum AMH level seems to be more strongly related to the ovarian reserve and to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B or estradiol, which are more commonly used markers. Our study involving 69 women undergoing a cycle of in vitro fertilisation (IVF) or intracytoplamic sperm injection (ICSI) treatment, confirmed these results. We have shown in this study that AMH is significantly correlated with the number of eggs collected and is of great interest as a negative predictive value for the success of assisted reproductive technology (ART). Further studies are needed to determine AMH cut-off values.
Assuntos
Glicoproteínas/fisiologia , Técnicas de Reprodução Assistida , Hormônios Testiculares/fisiologia , Hormônio Antimülleriano , Feminino , Regulação da Expressão Gênica , Glicoproteínas/genética , Humanos , Masculino , Ovário/fisiologia , Ovulação , Gravidez , Hormônios Testiculares/genéticaRESUMO
Anti-Müllerian hormone (AMH), produced by gonadal somatic cells, is mainly responsible for the regression of Müllerian ducts--the anlagen of uterus and Fallopian tubes--during male sex differentiation. Like other members of the transforming growth factor beta (TGF-beta) family, AMH signals through two serine/threonine kinase receptors, of which type II is specific, and type I is shared with the bone morphogenetic protein family. Persistent Müllerian duct syndrome is a rare form of male pseudohermaphroditism characterized by the persistence of Müllerian derivatives in otherwise normally virilized males. It is transmitted according to a recessive autosomic pattern and is due, in 84% of cases, to mutations of AMH and AMH receptor type II genes. Serum AMH is normal for age in patients with AMH type II mutations and low or undetectable in those with AMH mutations. In 14% of cases the origin of the condition is unknown.
Assuntos
Transtornos do Desenvolvimento Sexual/genética , Ductos Paramesonéfricos/anormalidades , Receptores de Peptídeos/genética , Animais , Hormônio Antimülleriano , Criptorquidismo/patologia , Feminino , Genes Recessivos , Glicoproteínas/sangue , Glicoproteínas/fisiologia , Humanos , Masculino , Ductos Paramesonéfricos/efeitos dos fármacos , Mutação , Receptores de Fatores de Crescimento Transformadores beta , Transdução de Sinais , Síndrome , Hormônios Testiculares/sangue , Hormônios Testiculares/fisiologiaRESUMO
Anti-Müllerian hormone (AMH), a member of the TGF-beta family, plays a crucial role during male sexual differentiation. This paper reviews the role of anti-Müllerian hormone in the ovary. In vivo and in vitro studies showed that AMH has an inhibitory effect on primordial follicle recruitment and it decreases the sensitivity of follicles for the FSH-dependent selection for dominance. Besides its functional role in the ovary, the AMH serum level serves as an excellent candidate marker of ovarian reserve.
Assuntos
Glicoproteínas/fisiologia , Folículo Ovariano/fisiologia , Hormônios Testiculares/fisiologia , Adulto , Hormônio Antimülleriano , Feminino , Hormônio Foliculoestimulante/fisiologia , Glicoproteínas/sangue , Humanos , Ovário/fisiologia , Hormônios Testiculares/sangueRESUMO
Anti-Müllerian hormone (AMH), also called MUllerian inhibiting substance (MIS) is a product of supporting gonadal Sertoli and granulosa cells. Its main physiological role is the induction of regression of Müllerian ducts in male fetuses but it also plays a role in Leydig cell steroidogenesis and in follicular development. It is a member of the transforming growth factor B family and signals through two serine/threonine kinase receptors, only one of whom, type II, is specific. Type I receptors and the intracytoplasmic signaling molecules are shared with the bone morphogenetic family. AMH is positively regulated by SF1, SOX9 and FSH. Testosterone is a powerful downregulator. Males lacking functional AMH or AMH receptor genes do not undergo regression of MUllerian derivatives during fetal life. AMH is an excellent marker of prepubertal testicular function and has gained recognition as a valuable marker of follicular reserve in adult women.
Assuntos
Glicoproteínas/genética , Glicoproteínas/fisiologia , Transtornos Gonadais/diagnóstico , Hormônios Testiculares/genética , Hormônios Testiculares/fisiologia , Testículo/embriologia , Testículo/fisiologia , Animais , Hormônio Antimülleriano , Biomarcadores , Criança , Feminino , Transtornos Gonadais/genética , Transtornos Gonadais/fisiopatologia , Humanos , Masculino , Diferenciação Sexual/genéticaAssuntos
Transtornos do Desenvolvimento Sexual , Ductos Paramesonéfricos/anormalidades , Hormônio Antimülleriano , Diagnóstico Diferencial , Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/etiologia , Transtornos do Desenvolvimento Sexual/fisiopatologia , Transtornos do Desenvolvimento Sexual/terapia , Feminino , Glicoproteínas/biossíntese , Glicoproteínas/fisiologia , Humanos , Células Intersticiais do Testículo , Masculino , Prognóstico , Células de Sertoli/metabolismo , Hormônios Testiculares/biossíntese , Hormônios Testiculares/fisiologia , Procedimentos Cirúrgicos UrológicosRESUMO
Conventional wisdom holds that gonadal steroid hormones organize and sexually differentiate neural circuits perinatally, and at puberty they activate these circuits to facilitate expression of social behaviors. Using the Syrian hamster to study the role of pubertal hormones in behavioral maturation, we have found that pubertal hormones also organize the adolescent brain. Initial studies revealed that male reproductive behavior cannot be activated by gonadal steroids prepubertally, indicating that the brain acquires behavioral responsiveness during adolescence. Subsequent experiments demonstrated that the presence of gonadal hormones during adolescence masculinize and defeminize behavioral responses of males to hormones in adulthood. Preliminary data also suggest that ovarian hormones defeminize but do not masculinize behavioral responses of females to hormones in adulthood. Furthermore, pubertal hormones program the adult expression of agonistic behaviors that are both steroid-dependent and steroid-independent in adulthood. Thus, the interaction between pubertal hormones and the adolescent brain is key for the maturation of adult social behaviors, and perturbations in the timing of this interaction have long-lasting consequences on adult behavior.
Assuntos
Puberdade/psicologia , Maturidade Sexual/fisiologia , Comportamento Social , Adolescente , Comportamento Agonístico/fisiologia , Animais , Cricetinae , Feminino , Hormônios Gonadais/fisiologia , Humanos , Masculino , Mesocricetus , Ovário/metabolismo , Comportamento Reprodutivo/fisiologia , Hormônios Testiculares/fisiologiaRESUMO
BACKGROUND: Anti-Müllerian hormone (AMH) inhibits the initiation of the development and early growth of mouse ovarian follicles. Furthermore, the ovarian follicle pool diminishes prematurely in AMH-knockout mice. In this study, we examined whether AMH plays a similar role in humans, controlling ovarian follicle growth. METHODS: Human ovarian cortical tissue biopsy specimens were cut into small pieces and cultured for 7 days in medium containing rat recombinant AMH at 0, 10, 30 or 100 ng/ml. The developmental stages and viability of the follicles were evaluated from histological sections. RESULTS: Similar to previous studies, significant initiation of follicle growth was observed in almost all culture media, as demonstrated by a significantly smaller proportion of primordial follicles (14-26%) compared with non-cultured control tissue (56%). The exception was tissue in medium supplemented with AMH at 100 ng/ml. Here, the proportion of primordial follicles was not significantly different from that in non-cultured tissue; furthermore, it was significantly greater than that in vehicle control cultures and cultures containing AMH at 10 ng/ml, indicating the inhibition of growth initiation. Viability was unaffected by the presence of AMH when compared with tissues in control media. CONCLUSIONS: Recombinant AMH at a concentration of 100 ng/ml has an inhibitory effect on early human ovarian follicular development in vitro, suppressing the initiation of primordial follicle growth.
Assuntos
Glicoproteínas/fisiologia , Folículo Ovariano/metabolismo , Ovário/metabolismo , Hormônios Testiculares/fisiologia , Adulto , Animais , Hormônio Antimülleriano , Técnicas de Cultura de Células/métodos , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Knockout , RatosRESUMO
After testis formation, further development of a male phenotype (masculinization) is driven by three hormones from the foetal testis: anti-Müllerian hormone, insulin-like factor 3, and testosterone. These hormones divert the development of reproductive and other organs from female to male and also play a role in testis development. The hormone dependence of masculinization renders this process inherently susceptible to disruption by factors that interfere with hormone production, bioavailability, metabolism, or action. This susceptibility is illustrated by the high prevalence of congenital masculinization disorders (cryptorchidism, hypospadias) and disorders in young adult men (low sperm counts, testis cancer), which may also stem from maldevelopment (dysgenesis) of the foetal testis. Testicular dysgenesis occurring in humans, or which is induced in animal models by foetal exposure to certain phthalates, is associated with impaired hormone production by the foetal testis. There is currently no definitive evidence that exposure of humans to environmental chemicals can induce testicular dysgenesis and/or impair masculinization, though pathways via which this could potentially occur are established.
Assuntos
Disruptores Endócrinos/toxicidade , Glândulas Endócrinas/efeitos dos fármacos , Disgenesia Gonadal/induzido quimicamente , Diferenciação Sexual/efeitos dos fármacos , Animais , Hormônio Antimülleriano , Glicoproteínas/fisiologia , Humanos , Insulina/fisiologia , Masculino , Proteínas/fisiologia , Receptores Androgênicos/efeitos dos fármacos , Receptores de Estrogênio/efeitos dos fármacos , Processos de Determinação Sexual , Globulina de Ligação a Hormônio Sexual/biossíntese , Hormônios Testiculares/fisiologia , Testículo/efeitos dos fármacos , Testículo/embriologia , Testículo/patologia , Testosterona/fisiologiaRESUMO
The survival of motor neurons is controlled by multiple factors that regulate different aspects of their physiology. The identification of these factors is important because of their relationship to motor neuron disease. We investigate here whether Mullerian Inhibiting Substance (MIS) is a motor neuron survival factor. We find that motor neurons from adult mice synthesize MIS and express its receptors, suggesting that mature motor neurons use MIS in an autocrine fashion or as a way to communicate with each other. MIS was observed to support the survival and differentiation of embryonic motor neurons in vitro. During development, male-specific MIS may have a hormone effect because the blood-brain barrier has yet to form, raising the possibility that MIS participates in generating sex-specific differences in motor neurons.
Assuntos
Glicoproteínas/fisiologia , Neurônios Motores/fisiologia , Hormônios Testiculares/fisiologia , Animais , Hormônio Antimülleriano , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/análise , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Sobrevivência Celular , Células Cultivadas , Glicoproteínas/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/análise , Receptores de Peptídeos/genética , Receptores de Peptídeos/fisiologia , Receptores de Fatores de Crescimento Transformadores beta , Diferenciação Sexual , Hormônios Testiculares/genéticaRESUMO
The complex mechanisms are responsible for male sex determination and differentiation. The steps of formation of the testes are dependent on a series of Y-linked, X-linked and autosomal genes actions and interactions. After formation of testes the gonads secrete hormones, which are essential for the formation of the male genitalia. Hormones are transcription regulators, which function by specific receptors. Ambiguous genitalia are result of disruption of genetic interaction. This review describes the mechanisms, which lead to differentiation of male sex and ways by which the determination and differentiation may be interrupted by naturally occurring mutations, causing different syndromes and diseases.
Assuntos
Transtornos do Desenvolvimento Sexual/genética , Processos de Determinação Sexual , Diferenciação Sexual , Adolescente , Adulto , Androgênios/biossíntese , Androgênios/fisiologia , Deleção Cromossômica , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Mutação , Gravidez , Diferenciação Sexual/genética , Diferenciação Sexual/fisiologia , Hormônios Testiculares/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Transcrição Gênica , Virilismo/genéticaRESUMO
The first critical transition in follicular development, the activation of primordial follicles to leave the pool of resting follicles and begin growth, is poorly understood, but it appears that the balance between inhibitory and stimulatory factors is important in regulating the exodus of follicles from the resting pool. There is evidence that anti-Mullerian hormone (AMH; also known as MIS) inhibits follicle activation in mice, but whether it plays a similar role in non rodent species is not known. When pieces of bovine ovarian cortex, rich in primordial follicles, are cultured in serum-free medium, most follicles initiate growth, but when cortical pieces are grafted beneath the chorioallantoic membrane (CAM) of chick embryos, follicle activation does not occur. Since embryonic chick gonads of both sexes produce and secrete high levels of AMH, the hypothesis that the AMH in the chick circulation inhibits follicle activation was tested. In Experiment 1, whole newborn mouse ovaries were grafted beneath the CAM (placed "in ovo") or cultured in vitro for 8 days. In vitro (or after 8 days in vivo) follicles activated and proceeded to the primary or secondary stage, but activation was suppressed in ovo. This inhibition was reversed if ovaries were removed from beneath the CAM and cultured in vitro. In contrast, when ovaries from mice null mutant for the AMH type II receptor were CAM-grafted in Experiment 2, follicle activation occurred in a similar fashion to activation in vitro. This finding strongly implicates AMH as the inhibitor of follicle activation in ovo. Since chick embryonic gonads are the source of circulating AMH, chicks were gonadectomized in Experiment 3, prior to grafting of pieces of bovine ovarian cortex beneath their CAMs. Bovine primordial follicles activated in the gonadectomized chicks, similar to the results for mice lacking the AMH type II receptor. Taken together these experiments provide strong evidence that AMH is the inhibitor of mouse follicle activation present in the circulation of embryonic chicks and provide indirect, and hence more tentative, evidence for AMH as an inhibitor of bovine follicle activation.
Assuntos
Membrana Corioalantoide/fisiologia , Glicoproteínas/fisiologia , Folículo Ovariano/fisiologia , Hormônios Testiculares/fisiologia , Animais , Hormônio Antimülleriano , Bovinos , Embrião de Galinha , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Orquiectomia , Folículo Ovariano/anatomia & histologia , Ovariectomia , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Receptores de Fatores de Crescimento Transformadores betaRESUMO
Anti-Müllerian hormone (AMH) produced by fetal Sertoli cells is responsible for regression of Müllerian ducts, the anlage for uterus and Fallopian tubes, during male sex differentiation. A member of the transforming growth factor-beta superfamily, AMH signals through two transmembrane receptors, type II which is specific and type I receptors, shared with the bone morphogenetic protein family. Mutations of the AMH and AMH receptor type II (AMHR-II) genes lead to persistence of the uterus and Fallopian tubes in males. Both conditions are transmitted according to a recessive autosomal pattern and are symptomatic only in males. Affected individuals are otherwise normally virilized, undergo normal male puberty; and may be fertile if testes, tightly attached to the Fallopian tubes, can be replaced in the scrotum. Approximately 85% of the cases are due, in similar proportions, to mutations of the AMH or AMHR-II gene. The genetic background does not influence the phenotype, the only difference is the level of circulating AMH which is normal for age in AMHR-II mutants and usually low or undetectable in AMH gene defects. This is due to lack of secretion, explained by the localization of the mutations in critical regions, based on the assumed 3D structure of the molecule. Similarly, lack of translocation to the surface membrane is responsible for the inactivity of AMHR-II molecules bearing mutations in the extracellular domain. In 15% of cases, the cause of the persistent Mullerian duct syndrome is unknown and could be related to complex malformations of the urogenital region, unrelated to AMH physiology.