AntiMullerian Hormone (AMH)

Introduction

The development of a foetus into a male or female individual is dependent on the sex chromosomes it carries. During early embryonic development, however, all fetuses have phenotypically female genitalia. Eventually, at the 6th or 7th week of pregnancy, a gene present on the XY chromosome leads to the development of the fetus into a male. A hormone that takes part in this differentiation is the Anti-Mullerian Hormone (AMH). This hormone, as the name suggests, works to regress the Mullerian Ducts in the male foetus. The Mullerian ducts, also known as the Paramesonephric Ducts, eventually give rise to the female reproductive organs, namely the fallopian tube, the uterus, the cervix and the upper region of the vagina.

Let us learn more about this hormone and its significance in males and females

What is the Anti-Mullerian Hormone?

The Anti-Mullerian Hormone or AMH is a glycoprotein hormone secreted by the Sertoli cells in males, or by the ovarian follicles in females. This hormone causes inhibition of the Mullerian Ducts in the male embryo. It is also known as the Mullerian Inhibiting Factor (MIF) or the Mullerian Inhibiting Substance (MIS).

Role of Anti-Mullerian Hormone

Anti-Mullerian Hormone inhibits the formation of the Mullerian ducts in the male embryo. The Mullerian Ducts are tissues formed in the fetus that give rise to the female reproductive tract. The FRT further develops into the oviducts, the uterus, the cervix and the vagina. In females, the AMH also represses the primordial follicle recruitment by the follicle-stimulating hormone (FSH).

The AMH is important in the development of the sex organs in a foetus.

Significance of Anti-Mullerian Hormone

• The expression of the Anti-Mullerian Hormone in the fetus determines the sexual differentiation of the fetus. Its expression occurs at a specific time during embryonic development.

• In males, AMH secreted by the Sertoli cells suppresses the Mullerian ducts from developing into the female reproductive tract. Hence, the level of AMH in the blood is a marker of the proper functioning of the Sertoli cells

• The AMH test measures the amount of AMH present in the blood. After puberty, the blood levels of AMH are used as an indication of fertility, menstrual disorders and ovarian cancer. In males, AMH

• In females, the AMH is secreted by the growing granulosa cells of the ovaries. Hence, AMH levels in the blood could indicate the size of the primordial cell pool left in the ovarian reserve, making the AMH test a biomarker of ovarian ageing

• AMH levels indicate the ability of a woman to get pregnant, as AMH is indicative of the number of eggs left in the ovary that can be fertilised. This is known as the ovarian reserve.

• High levels of AMH in the blood indicate a high ovarian reserve, implying a greater ability of the woman to conceive. On the other hand, low levels of AMH imply a depleting ovarian reserve, which further indicates low chances of getting pregnant

Hence, women who are facing trouble in conceiving, are often prescribed an AMH test.

Additionally, the levels of AMH in the blood of females are also used as−

• Indication of the beginning of menopause

• Detection of causes of amenorrhea.

• Diagnosis of Polycystic Ovarian Syndrome (PCOS), which disrupts the ability of a woman to get pregnant, among other things

• Monitoring the levels of AMH during ovarian cancer and its chemotherapy help in the detection and determination of whether treatments are effective

Influence of AMH on the development of males

• In male foetuses (i.e., those foetuses which carry the XY chromosome), the production of the anti-mullerian hormone is high. This promotes the development of the male sex organs by testosterone and represses the formation of the female reproductive tract.

• The secretion of AMH is stimulated by the Follicle Stimulating Hormone, which binds to receptors on the Sertoli cells. The AMH then binds to its receptors known as AMH type II receptors, further inducing the apoptosis of the fetal cells of the Mullerian Ducts.

• Low levels of AMH in male infants cause the genitals to not be fully male or female. This condition is referred to as pseudohermaphroditism or Persistent Mullerian duct syndrome. This condition may be a result of some mutations in the AMH genes or the genes of its receptors

• The secretion of AMH is stimulated by the Follicle Stimulating Hormone, which binds to receptors on the Sertoli cells. The AMH then binds to its receptors known as AMH type II receptors, further inducing the apoptosis of the fetal cells of the Mullerian Ducts.

• Persistent Mullerian Duct Syndrome leads to the development of female reproductive organs including the uterus, and the fallopian tubes. Such individuals have a fully functional male reproductive system. However, such males may suffer from cryptorchidism, which may cause inguinal hernia as well.

Influence of AMH on the development of females

• If the foetus has XX genes (assigned female at birth), a lesser amount of Anti-Mullerian hormone is produced. This permits the development of the Mullerian ducts, and subsequently, the formation of the oviducts, the uterus, the cervix and the upper part of the vagina

• The anti-Mullerian hormone, when secreted from the ovaries, inhibits the stimulation of the primordial follicles to transform into the primary follicles

• As seen in gene knockout experiments, the absence of the anti-Mullerian hormone leads to quicker recruitment of primordial follicles, and subsequent quicker exhaustion of the primary follicles, much before it happens in the wild-type animals

• As expected, the anti-mullerian hormone also exerts an inhibitory effect on the FSH activity

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Low levels of AMH are common in post-menopausal women and pre-puberty girls. The levels of the Anti-Mullerian Hormone are the highest during adolescence in girls. It reaches its maximum levels at 22-25 years of age

Conclusion

• The Anti-Mullerian Hormone (or AMH) is a crucial hormone that determines the development of the reproductive organs in both males and females

• In males, the Sertoli cells secrete the AMH, after stimulation by the Follicle Stimulating Hormone

• In males, the secretion of the AMH inhibits the development of Mullerian ducts. The Mullerian ducts develop into the female reproductive tract, including the uterus and the fallopian tube

• In females, the AMH is expressed by the granulosa cells in the early stages of folliculogenesis

• In females, the levels of AMH in the blood are indicative of the ability to get pregnant, or the window remaining for a couple to conceive.

• High levels of AMH in males are indicative of Persistent Mullerian Duct Syndrome

FAQs

Q1. How is Polycystic Ovarian Syndrome related to AMH?

Ans. High levels of AMH in a woman may be indicative of PCOS

Q2. What levels of AMH are considered normal?

Ans. In females, 1.0-3.0 ng AMH per millilitre of blood is considered normal

Q3. When is the Anti-Mullerian Hormone expressed in females?

Ans. In females, the expression of the Anti-Mullerian Hormone begins during the 25th week of pregnancy and goes on till the attainment of menopause

Q4. Which follicles exhibit the highest levels of AMH expression?

Ans. The preantral and the Graafian follicles show the highest expression of the AMH

Q5. What is the ovarian reserve at the time of birth? How many follicles remain in adolescence?

Ans. Around 1-2 million primordial follicles are present at birth, and by the time the female reaches adolescence, only 400,000 remain

Q6. Is the AMH the same as Inhibin?

Ans. No. Although the two hormones belong to the same family i.e., transforming growth factor-𝜷, and have a similar structure, the AMH serves to regress the Mullerian ducts, while inhibin is involved in the negative feedback control of FSH

Q7. What is the effect of testosterone on AMH?

Ans. AMH levels decrease with an increase in testosterone, especially during puberty