Anti-Mullerian Hormone: Molecular Mechanism of Action

During early fetal development. the primitive urogenital system is bipotential and can develop into a male or female direction, depending on the chromosomal sex of the fetus. In this chapter, regulatory factors of sex determination and differentiation are described. The roles of two testicular hormones, testosterone and anti-Mullerian hormone (AMH), which are essential for proper differentiation of the internal genitalia, are discussed

AMH in PCOS: Controlling the ovary, placenta, or brain?

Polycystic ovary syndrome (PCOS) is a very heterogeneous disease of which the exact pathophysiological mechanisms remain unknown. In PCOS, serum anti-Müllerian hormone (AMH) levels are significantly increased. AMH is a member of the transforming growth factor β family and is expressed by growing follicles in the ovaries. In PCOS, the transcriptional regulation of AMH and AMHR2 is altered, increasing and prolonging its temporal expression pattern. Moreover, the recently discovered extragonadal effects of AMH suggest that there might be a crosstalk between the ovary–placenta–brain. This review summarizes the recent findings concerning AMH and its role in the etiology of PCOS

Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function

CONTEXT: Anti-müllerian hormone (AMH) is produced by granulosa cells of small, growing follicles in the ovary. Serum AMH levels strongly correlate with the number of growing follicles, and therefore AMH has received increasing attention as a marker for ovarian reserve. This review summarizes recent findings and limitations in the application of serum AMH in ovarian reserve assessment. EVIDENCE ACQUISITION: A PubMed search was conducted to find recent literature on the measurements and use of serum AMH as a marker for ovarian reserve. EVIDENCE SYNTHESIS: Serum AMH levels are measured to assess the "functional ovarian reserve," a term that is preferred over "ovarian reserve," since AMH levels reflect the pool of growing follicles that potentially can ovulate. Serum AMH levels are used in individualized follicle-stimulating hormone dosing protocols and may predict the r

Regulation of ovarian function: the role of anti-Mullerian hormone

Anti-Mullerian hormone (AMH), also known as Mullerian inhibiting substance, is a member of the transforming growth factor beta superfamily of growth and differentiation factors. In contrast to other members of the family, which exert a broad range of functions in multiple tissues, the principal function of AMH is to induce regression of the Mullerian ducts during male sex differentiation. However, the patterns of expression of AMH and its type II receptor in the postnatal ovary indicate that AMH may play an important role in ovarian folliculogenesis. This review describes several in vivo and in vitro studies showing that AMH participates in two critical selection points of follicle development: it inhibits the recruitment of primordial follicles into the pool of growing follicles and also decreases the responsiveness of growing follicles to FSH

Circulating steroid hormone variations throughout different stages of prostate cancer

Steroid hormones play a central role in the maintenance and progression of prostate cancer. The androgen receptor is the primary driver of tumor cell proliferation and is activated by the androgens testosterone and 5α-dihydrotestosterone. Inhibition of this pathway through medical or surgical castration improves survival in the majority of advanced prostate cancer patients. However, conversion of adrenal androgen precursors and alternative steroidogenic pathways have been found to contribute to tumor progression and resistance to treatment. The emergence of highly accurate detection methods allows us to study steroidogenic mechanisms in more detail, even after treatment with potent steroidogenic inhibitors such as the CYP17A1 inhibitor abiraterone. A clear overview of steroid hormone levels in patients throughout the local, metastatic and castration-resistant stages of prostate cancer and treatment modalities is key toward a better understanding of their role in tumor progression and treatment resistance. In this review, we summarize the currently available data on steroid hormones that have been implicated in the various stages of prostate cancer. Additionally, this review addresses the implications of these findings, highlights important studies in this field and identifies current gaps in literature

Sex difference in thermal preference of adult mice does not depend on presence of the gonads

Background: The thermoneutral zone (TNZ) is a species-specific range of ambient temperature (T a), at which mammals can maintain a constant body temperature with the lowest metabolic rate. The TNZ for an adult mouse is between 26 and 34 °C. Interestingly, female mice prefer a higher T a than male mice although the underlying mechanism for this sex difference is unknown. Here, we tested whether gonadal hormones are dominant factors controlling temperature preference in male and female mice. Methods: We performed a temperature preference test in which 10-week-old gonadectomized and sham-operated male and female C57BL/6J mice were allowed to choose to reside at the thermoneutral cage of 29 °C or an experimental cage of 26, 29, or 32 °C. Results: All mice preferred a T a higher than 26 °C, especially in the inactive phase. Choosing between 29 and 32 °C, female mice resided more at 32 °C while male mice had no preference between the temperatures. Hence, the preferred T a for female mice was significantly higher (0.9 ± 0.2 °C) than that for male mice. However, gonadectomy did not

Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

Background: In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed in BAT and are involved in BAT activity. We hypothesized that differential expression of BMPs and FGFs might contribute to sex differences in BAT activity. Methods: We investigated the expression of BMPs and FGFs in BAT of male and female C57BL/6J mice upon gonadectomy, cold exposure, and exposure to sex steroids. Results: Of the FGF family, BAT Fgf1, Fgf9, Fgf18, and Fgf21 expression was induced upon cold exposure, but only Fgf1 expression was obviously different between the sexes: females had 2.5-fold lower BAT Fgf1 than males. Cold exposure induced BAT Bmp4 and Bmp8b expression, but only Bmp8b differed between the sexes: females had 35-fold higher BAT Bmp8b than males. Ovariectomy almost completely blunted BAT Bmp8b expression, while orchidectomy had no effect. Male mice and ovariectomized female mice treated with diethylstilbestrol (DES) had approximately 350-fold and approximately 36-fold higher BAT Bmp8b expression, respectively. Ninety-day and 7-day treatment of female mice with dihydrotestosterone (DHT) decreased BAT Bmp8b expression by approximately fivefold and approximately fourfold, respectively. Finally, treatment of primary murine brown adipocytes with DES did not result in changes in Bmp8b expression. Conclusions: BAT Bmp8b expression in mice is positively regulated by presence of ovaries and estrogens such as DES

Back to the basics of ovarian aging: A population-based study on longitudinal anti-Müllerian hormone decline

Background: Anti-Müllerian hormone (AMH) is currently used as an ovarian reserve marker for individualized fertility counseling, but very little is known of individual AMH decline in women. This study assessed whether the decline trajectory of AMH is uniform for all women, and whether baseline age-specific AMH levels remain consistently high or low during this trajectory. Methods: A total of 3326 female participants from the population-based Doetinchem Cohort Study were followed with five visits over a 20-year period. Baseline age was 40±10years with a range of 20-59 years. AMH was measured in 12,929 stored plasma samples using the picoAMH assay (AnshLabs). Decline trajectories of AMH were studied with both chronological age and reproductive age, i.e., time to menopause. Multivariable linear mixed effects models characterized the individual AMH decline trajectories. Results: The overall rate of AMH decline accelerated after 40years of age. Mixed models with varying age-specific AMH levels and decline rates provided the significantly best fit to the data, indicating that the fall in AMH levels over time does not follow a fixed pattern for individual women. AMH levels remained consistent along individual trajectories of age, with an intraclass correlation coefficient (ICC) of 0.87. The ICC of 0.32 for AMH trajectories with time to menopause expressed the large variation in AMH levels at a given time before the menopause. The differences between low and high age-specific AMH levels remained distinguishable, but became increasingly smaller with increasing chronological and reproductive age. Conclusions: This is the first study to characterize individual AMH decline over a long time period and broad age range. The varying AMH decline rates do not support the premise of a uniform AMH decline trajectory. Although age-specific AMH levels remain consistently high or low with increasing age, the converging trajectories and variance of AMH levels at a given time before menopause shed doubt on the added value of AMH to represent individualized reproductive age

The tyrosine kinase inhibitor sunitinib affects ovulation but not ovarian reserve in mouse: A preclinical study

The aim of the study was to evaluate ovarian toxicity of tyrosine kinase inhibitor (TKI) sunitinib, since only scarce data are available on gonadal function after this treatment. Six-weekold female mice received orally, once daily, vehicle or sunitinib (50 mg/kg/d) during 5 weeks. Fertility parameters were analyzed from ovulation to litter assessment. Sunitinib exposure significantly reduced (i) corpora lutea number per ovary (1.1 ± 0.38 in sunitinib group versus 4 ± 0.79 in control group, p<0.01) and (ii) serum Anti Müllerian hormone (AMH) levels in sunitinib treated mice (12.01 ± 1.16) compared to control mice (14.33 ± 0.87 ng/ml, p< 0.05). However, primordial and growing follicles numbers per ovary were not different in both groups. After treatment withdrawal, female mice in both groups were able to obtain litters. These data could be helpful to counsel clinicians and patients, when fertility preservation methods are discussed, before TKI treatment in girls and young women

Decline of ovarian function in patients with rheumatoid arthritis: serum anti-Mullerian hormone levels in a longitudinal cohort

Objective Rheumatoid arthritis (RA) often affects women in their fertile age, and is known to compromise female fertility. Serum anti-Müllerian hormone (AMH) levels are a proxy for the total number of primordial follicles, and a reliable predictor of the age at menopause. Our objective was to study the longitudinal intra-individual decline of serum AMH levels in female RA patients. Methods Female RA patients from a nationwide prospective cohort (2002–2008) were re-assess