The anti-Mullerian hormone is a homodimeric glycoprotein belonging to the transforming growth factor p (TGF P) family. All members of this superfamilyare involved in the regulation of tissue growth and differentiation. Prior to secretion, the hormone undergoes glycosylation and dimerization to produce an approximately 140 kDa precursor of two identical disulfidelinked 70 kDa subunits. Each monomer contains a large N-terminal proregion and a much smaller C-terminal mature domain. In contrast to other TGF P family members, AMH is thought to require the N-terminal domain to potentiate activity of the C-terminal domain to attain full bioactivity.
A part of AMH is then cleaved at a specific site between the pro-region and the mature region during cytoplasmic transit to generate biologically active 110 kDa N-terminal and 25 kDa C-terminal homodimers which remain associated in a non-covalent complex. The AMH type II receptor (AMH RII) has the capacity of binding only the biologically active form of AMH. In males, AMH is secreted by the Sertoli cells of the testes. During
embryonic development in males, secretion of AMH from testicular Sertoli cells is responsible for the regression of the MOllerian duct and the normal development of the male reproductive tract. The secretion of AMH by the
Sertoli cells starts during the embryogenesis and continues throughout life.
AMH is continuously produced by the testicles until puberty and then decreases slowly to post-puberty values. In females AMH plays an important role in the ovarian folliculogenesis. Follicle development in the ovaries comprises two distinct stages: initial recruitment, by which primordial follicles start to mature, and cyclic
recruitment, which leads to the growth of a cohort of small antral follicles, among which the dominant follicle (destined to ovulate) is subsequently selected. FSH (follicle-stimulating hormone) directs the cyclic recruitment.
AMH expression in granulosa cells starts in primary follicles and is maximal in granulosa cells of preantral and small antral follicles up to approximately 6 mm in diameter. When follicle growth becomes FSH-dependent, AMH expression diminishes and becomes undetectable. This pattern of AMH expression supports the inhibitory role of AMH at two distinct stages of folliculogenesis. First, AMH inhibits the transition of follicles from primordial
into maturation stages and thereby has an important role in regulating the number of follicles remaining in the primordial pool. Second, AMH has inhibitory effects on follicular sensitivity to FSH and therefore has a role in
the process of follicular selection.
Serum levels of AMH are barely detectable at birth in females, reach their highest levels after puberty, decrease progressively thereafter with age, and become undetectable at menopause. Serum AMH levels have been shown to be relatively stable during the menstrual crcle with substantial fluctuations being observed in younger women. AMH levels further demonstrate lower intra- and inter-cyclic variation than baseline FSH.
Serum AMH levels decrease significantly during the use of combined contraceptives. Clinical applications of AMH measurements have been proposed for a variety of indications. Measurement of serum AMH is clinically mainly used for assessment of ovarian reserve reflecting the number of antral and pre-antral follicles, the so-called antral follicle count (AFC), and for the prediction of response to controlled ovarian. stimulation. Further clinical applications of AMH are diagnosis of disorders of sex development (DSD) in children and monitoring of granulosa cell tumors to detect residual or recurrent disease. AMH has been suggested as a surrogate biomarker for AFC in the diagnosis of polycystic ovarv syndrome (PCOS} and for the prediction of time to
Manufacturer’s reagent package insert, Elecsys and cobas e analyzers AMH, 2019-02, V 6.0 , Roche Diagnostics GmbH, D-68305 Mannheim