Follicle stimulating hormone (FSH) comprises an ?? subunit and a ?? subunit,whereas the FSH receptor consists of two halves with distinct functions, the N-terminalextracellular exodomain and C-terminal membrane associated endodomain. FSH initiallybinds to exodomain, and the resulting FSH/exodomain complex modulates the endodomainand generates signal. However, it has been difficult to determine which subunit of FSHcontacts the exodomain or endodomain, and in what orientation FSH interacts with them.To address these crucial issues, the receptor was Ala-scanned and the hormone subunitswere probed with photoaffinity labeling with receptor peptides corresponding to the Nterminalregion of the exodomain and exoloop 3 of the endodomain. The results show thatboth regions of the receptors are important for hormone binding and signal generation. Inaddition, the FSH ?? subunit is specifically labeled with the N-terminal peptide, whereas the?? subunit is labeled with the exoloop 3 peptide. These contrasting results show that the FSH?? subunit is close to the N-terminal region and the ?? subunit is projected toward exoloop 3in the endodomain. The results raise the fundamental question whether the ?? subunit,common among the glycoprotein hormones, plays a major role in generating the hormonesignal common to all glycoprotein hormones.

Background: The ovarian response to follicle stimulating hormone (FSH) stimulation in assisted conception cycles is variable. Although it would be beneficial to predict accurately the response of patients to FSH, to date no robust predictors of ovarian performance have been identified. Recently, there have been a number of studies on the effect of single nucleotide polymorphisms (SNP) in the FSH receptor gene and its predictive value in the patients undergoing ovarian stimulation. Several reports have shown that two common SNPs at positions 307 and 680 in exon 10 of the FSH receptor gene are associated with ovarian response in in-vitro fertilization (IVF). Some authors have shown predictability of ovarian response to FSH stimulation in patients with different alleles, while others have refuted this finding. Until now, there is no clear clinical benefit in screening FSHR genotypes before IVF treatment. Objective: 1) To study the association between ovarian response and FSHR gene polymorphisms2) To study the association between FSHR gene polymorphisms and markers of ovarian reserve, including Anti Mullerian Hormone, Antral Follicle Count, Follicle Stimulating Hormone.Design: Prospective observational studyMethodology: 421 patients attending a tertiary reproductive medicine unit undergoing first cycle of IVF treatment were recruited into the study. Blood tests were taken on day 2 or 3 of the cycle for assessment of hormones and for DNA extraction. The SNP genotyping was done using Taqman analysis. Non-parametric tests were done to compare the various outcome parameters in patients with different genotypes.Results: FSHR p.Asn680Ser was not predictive of ovarian response. There was no evidence of any difference in basal FSH, AMH or AFC between the patients with different FSHR genotypes, with or without an adjustment for age or BMI. On subgroup analysis, there was no evidence that FSHR p.Asn680Ser genotypes are associated with PCOS, high AMH levels or response to clomiphene citrate. FSHR gene polymorphism was also not related to oocyte maturity or fertilization rate.Conclusions: FSHR p.Asn680Ser was not shown to be predictive of ovarian response, although clinically relevant differences cannot be ruled out. There may be an effect size but smaller than that detected for the power of this study. Other genetic markers may be relevant in the prediction of response to ovarian stimulation.

Daktaro disertacijos „Nėštumo laukimo laiką prognozuojančių veiksnių tyrimas“ tikslas - įvertinti nėštumo laukimo laiko sąsajas su demografiniais, socialiniais, gyvensenos, darbo, aplinkos ir genetiniais veiksniais ir sudaryti prognostinius jų įtakos modelius. Tyrimo uždaviniai: 1.Įvertinti demografinių, socialinių, gyvensenos, darbo ir gyvena–mosios aplinkos veiksnių sąsajas su nėštumo laukimo laiku. 2.Sudaryti svarbiausių demografinių, socialinių, gyvensenos, darbo ir gyvenamosios aplinkos veiksnių, kurie nulemia 12 mėnesių ir ilgesnį nėštumo laukimo laiką, prognostinį įvertinimo modelį. 3.Įvertinti FSH receptoriaus geno polimorfizmo variantų įtaką nėš–tumo laukimo laikui. 4.Sudaryti FSH receptoriaus geno polimorfizmo įtakos svarbiausiems demografiniams, socialiniams, gyvensenos, darbo ir gyvenamosios aplinkos veiksniams, kurie nulemia 12 mėnesių ir ilgesnį nėštumo laukimo laiką, prognostinį modelį. Nustatėme, kad svarbiausi nepriklausomi 12 mėnesių ir ilgesnį nėštumo laukimo laiką nulemiantys prognostiniai veiksniai yra 30 metų ir vyresnis amžius, anksčiau gydyti vaisingumo sutrikimai, ginekologinės ligos, kontracepcijos priemonių naudojimas iki nėštumo planavimo pradžios ir FSH receptoriaus geno SER/SER variantas, kurie pastojimo po 12 ir daugiau mėnesių tikimybę didino, atitinkamai, 1,95, 1,57, 2,21, 1,87 ir 1,68 kartus. / “Study of time to pregnancy prognostic factors”. The aim of the study was to investigate the relation between various factors and female fecundity, which was expressed as time to pregnancy (TTP) and to create prognostic models. Tasks of the study were: 1.Estimate the relation between socioeconomic, demographic, life-style, environmental and job-related factors and time to pregnancy; 2.Create prognostic valuation model for the most important social, demographic, life-style, environmental and job-related factors what are associated with 12 month or longer time to pregnancy; 3.Estimate the impact of FSH receptor gene polymorphism variant on time to pregnancy; 4.Create prognostic model for the most important factors what are associated with 12 month or longer time to pregnancy under the influence of FSH receptor gene polymorphism. We established, that the most important independent risk factors prognoses time to pregnancy of 12 or more months in women analyzed for FSH receptor gene polymorphism group were older age, having gynecological diseases or fertility problems in the past, the use of contraception prior to conception and SER/SER polymorphism variant, what increased the probability of conceiving after 12 or more months 1.95, 1.57, 2.21, 1.87 and 1.68 times respectively.

No description available.

A Osteoporose é uma doença esquelética caracterizada pelo comprometimento da resistência óssea predispondo a um risco aumentado de fraturas em mulheres na pósmenopáusa e na população idosa. O processo de remodelamento ósseo é mediado pela atividade dos osteoblastos na formação e a atividade dos osteoclastos na reabsorção da matriz óssea. Entre os vários fatores que modulam o processo de ressorção óssea estão os hormônios esteróides sexuais. Desta forma, a diminuição dos estrogênios circulantes, como ocorre na menopausa e na Falência Ovariana Prematura (FOP) resulta em uma maior perda da massa óssea. A FOP é uma condição definida como a falência da função ovariana antes dos 40 anos de idade, causando amenorréia, hipogonadismo e níveis elevados de gonadotrofinas. Vários estudos têm sugerido que esta falência gonadal possa ser uma doença genética, sendo o gene do receptor do FSH (FSHR), considerado um dos principais genes candidatos. Entretanto faltam estudos consistentes capazes de avaliar a influência destas variantes genéticas sobre a densidade mineral óssea assim como o risco de osteoporose. Assim, estudou-se uma coorte de 32 mulheres com FOP acompanhadas na Unidade de Endocrinologia Ginecológica, Serviço de Endocrinologia do Hospital de Clínicas de Porto Alegre, com os objetivos de determinar a freqüência de alterações na DMO e analisar uma possível associação entre variáveis hormonais e densidade mineral óssea comparando-as com um grupo de referência composto por 80 mulheres, sendo 25 mulheres na pré-menopausa (PRE-M) e 55 mulheres na pós-menopausa (POS-M). Também foi pesquisado se a presença de polimorfismos do gene do receptor do FSH estava associada com alterações na densidade mineral óssea no grupo FOP. Variáveis clínicas e hormonais foram obtidas, assim como a densitometria óssea foi realizada em todas as pacientes de ambos grupos, porém a análise da freqüência das variantes Ala307Thr e Ser680Asn do exon 10 do gene do FSHR foi realizada somente das pacientes do grupo FOP. A densitometria óssea de cada paciente foi classificada como massa óssea normal ou baixa massa óssea (osteopenia ou osteoporose) pelos critérios da OMS. O IMC apresentou correlação positiva com a DMO do fêmur total (p<0.05). A freqüência de baixa massa óssea foi significativamente maior no grupo FOP do que no grupo POS-M (p=0,042). Entretanto, quando a análise foi controlada pelo uso ou não de terapia hormonal, os grupos não apresentaram diferença significativa. Identificou-se maior freqüência de baixa massa óssea em L1-L4 no grupo FOP (p<0,001) enquanto o grupo de referência POS-M apresentou maior freqüência de baixa massa óssea no fêmur total (p<0,001). Não houve associação entre as variantes Ala307Thr e Ser680Asn do gene do FSH e a densidade mineral óssea (DMO em g/cm2) em coluna ou fêmur total. Concluindo, o grupo de pacientes com FOP apresentou maior frequência de alteraçoes na DMO, em especial em coluna, quando comparado com o grupo de referência na pós-menopausa. Embora os polimorfismos estudados no exon 10 do gene do FSHR possam modificar a ação do FSH, estas variantes genéticas parecem não ter influência sobre a DMO das pacientes com FOP. Entretanto, estudos longitudinais são necessários para confirmar os resultados do presente estudo. / Osteoporosis is a skeletal disease characterized by impairment of bone strength predisposing to an increased risk of fractures in postmenopausal women and in the elderly population. The process of bone remodeling is mediated by the activity of osteoblasts in the formation and activity of osteoclasts in the resorption of bone matrix. One of the factors modulating bone resorption is sex steroid hormones. Thus, the decline of circulating estrogens, as occurs in menopause and in premature ovarian failure (POF) results in greater loss of bone mass, POF is a condition defined as the failure of ovarian function before the age of 40 years, causing amenorrhea, hypogonadism and high levels of gonadotropins. Several studies have suggested that this gonadal failure can be a genetic disease, and the gene of the FSH receptor (FSHR), is considered as one of the leading candidate genes. Nonetheless, there is lacking studies that could consistently assess the influence of these genetic variants on the bone mineral density and the risk of osteoporosis. Therefore, a cohort of 32 women presenting POF and being followed at the Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clinicas de Porto Alegre, was studied, with the objectives of determining the frequency of changes on BMD and analyze a possible association between hormonal variables and BMD, compared to a reference group composed of 80 women, with 25 in pre-menopausal (PRE-M) and 55 women in post-menopausal (POS-M). There was also searched if the presence of FSH receptor polymorphisms was associated with changes in the in bone mineral density in the group of POF. Clinical and hormonal variables were obtained as well as bone densitometry was performed in all patients in both groups; however, the analysis of the frequency of Ala307Thr and Ser680Asn variants of exon 10 of the gene of FSHR was performed only in the group of POF. Bone densitometry of each patient was classified as normal bone mass or low bone mass (osteopenia or osteoporosis) by the WHO criteria. BMI showed a positive correlation with BMD of the total femur (p <0.05). The frequency of low bone mass was significantly higher in the group of POF patients than in the POS-M group (p = 0042). However, when the analysis was controlled by the use of hormonal therapy, the no statistical difference was observed. A higher frequency of low bone mass in L1-L4 was identified in the POF group (p <0001) while the reference group of POS-M showed higher frequency of low bone mass in the total femur (p <0001). There was no association between the Ala307Thr and Ser680Asn variants of the FSHR gene and bone mineral density (BMD in g/cm2) in L1-L4 or in femur total. In conclusion, POF group presented a higher frequency of changes on BMD, mainly in lumbar spine, when compared to the reference POS-M group. While the studied polymorphisms in the exon 10 of the FSHR gene may modify the FSH actions, these genetic variants appear to have no influence on BMD of these patients. However, longitudinal studies are needed to confirm the results of this study.

A Osteoporose é uma doença esquelética caracterizada pelo comprometimento da resistência óssea predispondo a um risco aumentado de fraturas em mulheres na pósmenopáusa e na população idosa. O processo de remodelamento ósseo é mediado pela atividade dos osteoblastos na formação e a atividade dos osteoclastos na reabsorção da matriz óssea. Entre os vários fatores que modulam o processo de ressorção óssea estão os hormônios esteróides sexuais. Desta forma, a diminuição dos estrogênios circulantes, como ocorre na menopausa e na Falência Ovariana Prematura (FOP) resulta em uma maior perda da massa óssea. A FOP é uma condição definida como a falência da função ovariana antes dos 40 anos de idade, causando amenorréia, hipogonadismo e níveis elevados de gonadotrofinas. Vários estudos têm sugerido que esta falência gonadal possa ser uma doença genética, sendo o gene do receptor do FSH (FSHR), considerado um dos principais genes candidatos. Entretanto faltam estudos consistentes capazes de avaliar a influência destas variantes genéticas sobre a densidade mineral óssea assim como o risco de osteoporose. Assim, estudou-se uma coorte de 32 mulheres com FOP acompanhadas na Unidade de Endocrinologia Ginecológica, Serviço de Endocrinologia do Hospital de Clínicas de Porto Alegre, com os objetivos de determinar a freqüência de alterações na DMO e analisar uma possível associação entre variáveis hormonais e densidade mineral óssea comparando-as com um grupo de referência composto por 80 mulheres, sendo 25 mulheres na pré-menopausa (PRE-M) e 55 mulheres na pós-menopausa (POS-M). Também foi pesquisado se a presença de polimorfismos do gene do receptor do FSH estava associada com alterações na densidade mineral óssea no grupo FOP. Variáveis clínicas e hormonais foram obtidas, assim como a densitometria óssea foi realizada em todas as pacientes de ambos grupos, porém a análise da freqüência das variantes Ala307Thr e Ser680Asn do exon 10 do gene do FSHR foi realizada somente das pacientes do grupo FOP. A densitometria óssea de cada paciente foi classificada como massa óssea normal ou baixa massa óssea (osteopenia ou osteoporose) pelos critérios da OMS. O IMC apresentou correlação positiva com a DMO do fêmur total (p<0.05). A freqüência de baixa massa óssea foi significativamente maior no grupo FOP do que no grupo POS-M (p=0,042). Entretanto, quando a análise foi controlada pelo uso ou não de terapia hormonal, os grupos não apresentaram diferença significativa. Identificou-se maior freqüência de baixa massa óssea em L1-L4 no grupo FOP (p<0,001) enquanto o grupo de referência POS-M apresentou maior freqüência de baixa massa óssea no fêmur total (p<0,001). Não houve associação entre as variantes Ala307Thr e Ser680Asn do gene do FSH e a densidade mineral óssea (DMO em g/cm2) em coluna ou fêmur total. Concluindo, o grupo de pacientes com FOP apresentou maior frequência de alteraçoes na DMO, em especial em coluna, quando comparado com o grupo de referência na pós-menopausa. Embora os polimorfismos estudados no exon 10 do gene do FSHR possam modificar a ação do FSH, estas variantes genéticas parecem não ter influência sobre a DMO das pacientes com FOP. Entretanto, estudos longitudinais são necessários para confirmar os resultados do presente estudo. / Osteoporosis is a skeletal disease characterized by impairment of bone strength predisposing to an increased risk of fractures in postmenopausal women and in the elderly population. The process of bone remodeling is mediated by the activity of osteoblasts in the formation and activity of osteoclasts in the resorption of bone matrix. One of the factors modulating bone resorption is sex steroid hormones. Thus, the decline of circulating estrogens, as occurs in menopause and in premature ovarian failure (POF) results in greater loss of bone mass, POF is a condition defined as the failure of ovarian function before the age of 40 years, causing amenorrhea, hypogonadism and high levels of gonadotropins. Several studies have suggested that this gonadal failure can be a genetic disease, and the gene of the FSH receptor (FSHR), is considered as one of the leading candidate genes. Nonetheless, there is lacking studies that could consistently assess the influence of these genetic variants on the bone mineral density and the risk of osteoporosis. Therefore, a cohort of 32 women presenting POF and being followed at the Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clinicas de Porto Alegre, was studied, with the objectives of determining the frequency of changes on BMD and analyze a possible association between hormonal variables and BMD, compared to a reference group composed of 80 women, with 25 in pre-menopausal (PRE-M) and 55 women in post-menopausal (POS-M). There was also searched if the presence of FSH receptor polymorphisms was associated with changes in the in bone mineral density in the group of POF. Clinical and hormonal variables were obtained as well as bone densitometry was performed in all patients in both groups; however, the analysis of the frequency of Ala307Thr and Ser680Asn variants of exon 10 of the gene of FSHR was performed only in the group of POF. Bone densitometry of each patient was classified as normal bone mass or low bone mass (osteopenia or osteoporosis) by the WHO criteria. BMI showed a positive correlation with BMD of the total femur (p <0.05). The frequency of low bone mass was significantly higher in the group of POF patients than in the POS-M group (p = 0042). However, when the analysis was controlled by the use of hormonal therapy, the no statistical difference was observed. A higher frequency of low bone mass in L1-L4 was identified in the POF group (p <0001) while the reference group of POS-M showed higher frequency of low bone mass in the total femur (p <0001). There was no association between the Ala307Thr and Ser680Asn variants of the FSHR gene and bone mineral density (BMD in g/cm2) in L1-L4 or in femur total. In conclusion, POF group presented a higher frequency of changes on BMD, mainly in lumbar spine, when compared to the reference POS-M group. While the studied polymorphisms in the exon 10 of the FSHR gene may modify the FSH actions, these genetic variants appear to have no influence on BMD of these patients. However, longitudinal studies are needed to confirm the results of this study.

A Osteoporose é uma doença esquelética caracterizada pelo comprometimento da resistência óssea predispondo a um risco aumentado de fraturas em mulheres na pósmenopáusa e na população idosa. O processo de remodelamento ósseo é mediado pela atividade dos osteoblastos na formação e a atividade dos osteoclastos na reabsorção da matriz óssea. Entre os vários fatores que modulam o processo de ressorção óssea estão os hormônios esteróides sexuais. Desta forma, a diminuição dos estrogênios circulantes, como ocorre na menopausa e na Falência Ovariana Prematura (FOP) resulta em uma maior perda da massa óssea. A FOP é uma condição definida como a falência da função ovariana antes dos 40 anos de idade, causando amenorréia, hipogonadismo e níveis elevados de gonadotrofinas. Vários estudos têm sugerido que esta falência gonadal possa ser uma doença genética, sendo o gene do receptor do FSH (FSHR), considerado um dos principais genes candidatos. Entretanto faltam estudos consistentes capazes de avaliar a influência destas variantes genéticas sobre a densidade mineral óssea assim como o risco de osteoporose. Assim, estudou-se uma coorte de 32 mulheres com FOP acompanhadas na Unidade de Endocrinologia Ginecológica, Serviço de Endocrinologia do Hospital de Clínicas de Porto Alegre, com os objetivos de determinar a freqüência de alterações na DMO e analisar uma possível associação entre variáveis hormonais e densidade mineral óssea comparando-as com um grupo de referência composto por 80 mulheres, sendo 25 mulheres na pré-menopausa (PRE-M) e 55 mulheres na pós-menopausa (POS-M). Também foi pesquisado se a presença de polimorfismos do gene do receptor do FSH estava associada com alterações na densidade mineral óssea no grupo FOP. Variáveis clínicas e hormonais foram obtidas, assim como a densitometria óssea foi realizada em todas as pacientes de ambos grupos, porém a análise da freqüência das variantes Ala307Thr e Ser680Asn do exon 10 do gene do FSHR foi realizada somente das pacientes do grupo FOP. A densitometria óssea de cada paciente foi classificada como massa óssea normal ou baixa massa óssea (osteopenia ou osteoporose) pelos critérios da OMS. O IMC apresentou correlação positiva com a DMO do fêmur total (p<0.05). A freqüência de baixa massa óssea foi significativamente maior no grupo FOP do que no grupo POS-M (p=0,042). Entretanto, quando a análise foi controlada pelo uso ou não de terapia hormonal, os grupos não apresentaram diferença significativa. Identificou-se maior freqüência de baixa massa óssea em L1-L4 no grupo FOP (p<0,001) enquanto o grupo de referência POS-M apresentou maior freqüência de baixa massa óssea no fêmur total (p<0,001). Não houve associação entre as variantes Ala307Thr e Ser680Asn do gene do FSH e a densidade mineral óssea (DMO em g/cm2) em coluna ou fêmur total. Concluindo, o grupo de pacientes com FOP apresentou maior frequência de alteraçoes na DMO, em especial em coluna, quando comparado com o grupo de referência na pós-menopausa. Embora os polimorfismos estudados no exon 10 do gene do FSHR possam modificar a ação do FSH, estas variantes genéticas parecem não ter influência sobre a DMO das pacientes com FOP. Entretanto, estudos longitudinais são necessários para confirmar os resultados do presente estudo. / Osteoporosis is a skeletal disease characterized by impairment of bone strength predisposing to an increased risk of fractures in postmenopausal women and in the elderly population. The process of bone remodeling is mediated by the activity of osteoblasts in the formation and activity of osteoclasts in the resorption of bone matrix. One of the factors modulating bone resorption is sex steroid hormones. Thus, the decline of circulating estrogens, as occurs in menopause and in premature ovarian failure (POF) results in greater loss of bone mass, POF is a condition defined as the failure of ovarian function before the age of 40 years, causing amenorrhea, hypogonadism and high levels of gonadotropins. Several studies have suggested that this gonadal failure can be a genetic disease, and the gene of the FSH receptor (FSHR), is considered as one of the leading candidate genes. Nonetheless, there is lacking studies that could consistently assess the influence of these genetic variants on the bone mineral density and the risk of osteoporosis. Therefore, a cohort of 32 women presenting POF and being followed at the Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clinicas de Porto Alegre, was studied, with the objectives of determining the frequency of changes on BMD and analyze a possible association between hormonal variables and BMD, compared to a reference group composed of 80 women, with 25 in pre-menopausal (PRE-M) and 55 women in post-menopausal (POS-M). There was also searched if the presence of FSH receptor polymorphisms was associated with changes in the in bone mineral density in the group of POF. Clinical and hormonal variables were obtained as well as bone densitometry was performed in all patients in both groups; however, the analysis of the frequency of Ala307Thr and Ser680Asn variants of exon 10 of the gene of FSHR was performed only in the group of POF. Bone densitometry of each patient was classified as normal bone mass or low bone mass (osteopenia or osteoporosis) by the WHO criteria. BMI showed a positive correlation with BMD of the total femur (p <0.05). The frequency of low bone mass was significantly higher in the group of POF patients than in the POS-M group (p = 0042). However, when the analysis was controlled by the use of hormonal therapy, the no statistical difference was observed. A higher frequency of low bone mass in L1-L4 was identified in the POF group (p <0001) while the reference group of POS-M showed higher frequency of low bone mass in the total femur (p <0001). There was no association between the Ala307Thr and Ser680Asn variants of the FSHR gene and bone mineral density (BMD in g/cm2) in L1-L4 or in femur total. In conclusion, POF group presented a higher frequency of changes on BMD, mainly in lumbar spine, when compared to the reference POS-M group. While the studied polymorphisms in the exon 10 of the FSHR gene may modify the FSH actions, these genetic variants appear to have no influence on BMD of these patients. However, longitudinal studies are needed to confirm the results of this study.

Abstract Anti-Müllerian hormone (AMH) was identified originally in connection with its role in male sexual differentiation. In females, AMH is secreted by ovarian granulosa cells of growing follicles and its serum levels correlate well with the remaining number of follicles, thus reflecting ovarian reserve. The aim of this study was to explore the expression and secretion of AMH in human ovarian development and in various disorders resulting in decreased reproductive function. In fetal ovaries, AMH expression was found to be initiated at midgestation and it increased gradually towards term. In serum samples from infant girls, transient postnatal activation of the pituitary-ovarian axis was found and it occurred later in premature infants, reflected in lower serum AMH levels and lower numbers of growing follicles. This immaturity resulted in insufficient feedback from ovary to pituitary and may explain the higher levels of follicle-stimulating hormone (FSH) in these girls. Ovarian follicle reserve is typically diminished in women with primary ovarian insufficiency (POI). Assay of serum AMH may be used to identify women with POI and existing follicles, as women with FSH receptor mutation who were known to have follicles had serum AMH levels in low normal range and girls/women with Turner syndrome mosaicism had higher serum AMH levels compared with those with other karyotypes. The diagnostics and follow-up of ovarian granulosa cell tumors (GCTs) are challenging as a result of the rarity of the disease and late possible recurrences. Assay of serum AMH combined with assay of the currently used marker inhibin B was shown to improve follow-up of GCTs in individual patients, compared with serum inhibin B measurement alone. The analyses revealed that AMH and inhibin B assays perform similarly in detecting macroscopic tumors. Continuous use of combined hormonal contraceptives inhibited ovarian activity independently of the administration route, as serum AMH levels decreased significantly and similarly during oral, transdermal or vaginal administration. The decrease of serum AMH levels indicates that AMH is secreted partially from FSH-dependent follicles. The study provides novel information on AMH secretion in ovarian development, and the use of AMH assay in assessing ovarian reserve and detecting ovarian disorders such as ovarian insufficiency and GCTs. / Tiivistelmä Naisen munasarjassa munarakkuloiden granuloosasolut erittävät anti-Müllerian hormonia (AMH), ja sen pitoisuudet seerumissa heijastavat jäljellä olevien munarakkuloiden määrää. Tässä tutkimuksessa tarkasteltiin AMH:n eritystä ja ilmentymistä munasarjan kehityksen aikana ja erilaisissa munasarjan toiminnan häiriötiloissa. Tuloksina havaittiin, että AMH:a ilmentyy sikiökaudella munasarjassa jo keskiraskaudesta eteenpäin. Syntymän jälkeen otetuissa seeruminäytteissä todettiin ohimenevä aivolisäkkeen ja munasarjan aktivaatio, joka ilmeni myöhemmin ennenaikaisesti syntyneillä tytöillä. Heillä havaittiin vähemmän kasvavia munarakkuloita ja matalammat seerumin AMH-pitoisuudet syntymän jälkeen kuin täysiaikaisilla tytöillä. Tämä kypsymättömyys johtui todennäköisesti munasarjan riittämättömästä palautejärjestelmästä aivolisäkkeeseen, mikä voi selittää korkeammat follikkelia stimuloivan hormonin (FSH) pitoisuudet ennenaikaisesti syntyneillä tytöillä. Ennenaikainen munasarjojen toiminnan hiipuminen voi johtua esim. kromosomi- tai geenivirheestä. Naisilla, joilla on virheellinen FSH-reseptori, tiedetään olevan munarakkuloita jäljellä, ja tulokset osoittivat seerumin AMH-pitoisuuksien olevan lähes normaali näillä naisilla. Myös tytöillä ja naisilla, joilla on todettu Turnerin oireyhtymän mosaikismi, AMH-pitoisuudet olivat merkittävästi korkeammat verrattuna muihin karyotyyppeihin. Täten AMH-määrityksen avulla voidaan mahdollisesti löytää ennenaikaisesta munasarjojen toiminnan hiipumisesta kärsivien joukosta ne naiset, joilla on vielä jäljellä munarakkuloita. Munasarjan granuloosasolukasvaimen diagnostiikka ja seuranta ovat haastavia kasvaimen myöhäisen uusiutumistaipumuksen ja harvinaisuuden vuoksi. Tulokset osoittivat, että seerumin AMH-määrityksen yhdistäminen tällä hetkellä käytössä olevaan inhibiini B -määritykseen voisi parantaa yksittäisten potilaiden seurantaa makroskooppisen kasvaimen toteamisen osalta. Tutkimus osoitti hormonaalisten yhdistelmäehkäisyvalmisteiden jatkuvan käytön vähentävän munasarjan aktiivisuutta merkittävästi annostelureitistä riippumatta, koska seerumin AMH-pitoisuudet laskivat samalla tavalla ehkäisypilleriä, -rengasta ja -laastaria käyttävillä naisilla. Tutkimus toi uutta tietoa AMH:n erityksestä munasarjan kehityksen aikana sekä AMH-määrityksen käytön mahdollisuuksista munarakkuloiden määrän arvioinnissa ja eri häiriötilojen tunnistamisessa.