anti-Müllerian Hormone mRNA Research Articles

Anti-müllerian hormone and anti-müllerian hormone type II receptor messenger ribonucleic acid expression during postnatal testis development and in the adult testis of the rat.

Anti-müllerian hormone (AMH) induces degeneration of the müllerian ducts during male sex differentiation and may have additional functions concerning gonadal development. In the immature rat testis, there is a marked developmental increase in AMH type II receptor (AMHRII) messenger RNA (mRNA) expression in Sertoli cells, concomitant with the initiation of spermatogenesis. AMHRII mRNA is also expressed at a high level in Sertoli cells in adult rats. To obtain information about the possible functions of AMH in the testis, we investigated the postnatal expression patterns of the genes encoding AMH and AMHRII in the rat testis in more detail. Using RNase protection assays, AMH and AMHRII mRNA expression was measured in total RNA preparations from testes or testicular tubule segments isolated from control rats and from rats that had received various treatments. The testicular level of AMHRII mRNA was found to be much higher than that of AMH mRNA in adult rats. AMH mRNA was detected at a maximal level at stage VII of the spermatogenic cycle and at a low level at the other stages. AMHRII mRNA increases from stage XIII, is highest at stages VI and VII, and then rapidly declines at stage VIII to almost undetectable levels at stages IX-XII. It was found that the increase in testicular AMHRII mRNA expression during the first 3 weeks of postnatal development also occurs in sterile rats (prenatally irradiated), and hence, is independent of the presence or absence of germ cells. Yet, the total testicular level of AMHRII mRNA was decreased in sterile adult rats (prenatally irradiated or experimental cryptorchidism), as compared with intact control rats. However, treatment of adult rats with methoxyacetic acid or hydroxyurea, which resulted in partial germ cell depletion, had no effect on total testicular AMHRII mRNA expression. We conclude that a combination of multiple spermatogenic cycle events, possibly involving changes of Sertoli cell structure and/or Sertoli cell-basal membrane interactions, regulate autocrine AMH action on Sertoli cells, in particular at stage VII of the spermatogenic cycle.

Anti-mullerian hormone and anti-mullerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth

During fetal development, anti-müllerian hormone (AMH) is produced only by Sertoli cells, but postnatally, granulosa cells also produce this peptide growth/differentiation factor. We recently identified a candidate AMH type II receptor (AMHRII). In the present study, postnatal ovarian AMH and AMHRII messenger RNA (mRNA) expression was studied by in situ hybridization and ribonuclease protection. In ovaries from adult rats, AMH and AMHRII mRNAs were found to be mainly expressed in granulosa cells from preantral and small antral follicles. Corpora lutea and large antral follicles express little or no AMH and AMHRII mRNA, and primordial follicles and oocytes appeared to be AMH and AMHRII mRNA negative. Thecal and interstitial cells express no detectable AMH mRNA and little or no AMHRII mRNA. The colocalization of AMH and AMHRII mRNAs in granulosa cells of specific follicle types suggests that actions of AMH via AMHRII are autocrine in nature. There is a decreased level of AMH and AMHRII mRNA expression when follicles become atretic. Both mRNA species are eventually lost from atretic follicles, although AMHRII mRNA expression seems to persist somewhat longer than AMH mRNA. During the estrous cycle, no marked changes in the patterns of AMH and AMHRII mRNA expression were detected, except at estrus, when expression of both mRNA species in preantral follicles was decreased compared to that on the other days of the cycle. On postnatal day 5, total ovarian AMH mRNA expression is low and is located in small preantral follicles. During the first weeks of postnatal development, AMH mRNA expression in preantral follicles increases, and the later formed small antral follicles also express AMH mRNA. In contrast, AMHRII mRNA is expressed on postnatal day 5 at a higher level than AMH mRNA, but cannot be localized to specific cell types. From postnatal day 15 onward, AMHRII mRNA expression becomes more restricted to the preantral and small antral follicles. Treatment of prepubertal rats with GnRH antagonist (Org 30276) and human recombinant FSH (Org 32489) or with GnRH antagonist and estradiol benzoate resulted in follicle growth and inhibition of AMH and AMHRII mRNA expression in some, but not all, preantral and small antral follicles. These results indicate that FSH and estrogens may play a role in the down-regulation of AMH and AMHRII mRNA expression in vivo when small antral follicles differentiate into large antral follicles. Furthermore, the FSH surge on the morning of estrus may inhibit AMH and AMHRII mRNA expression in preantral follicles.

Anti-müllerian hormone and anti-müllerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth.

During fetal development, anti-müllerian hormone (AMH) is produced only by Sertoli cells, but postnatally, granulosa cells also produce this peptide growth/differentiation factor. We recently identified a candidate AMH type II receptor (AMHRII). In the present study, postnatal ovarian AMH and AMHRII messenger RNA (mRNA) expression was studied by in situ hybridization and ribonuclease protection. In ovaries from adult rats, AMH and AMHRII mRNAs were found to be mainly expressed in granulosa cells from preantral and small antral follicles. Corpora lutea and large antral follicles express little or no AMH and AMHRII mRNA, and primordial follicles and oocytes appeared to be AMH and AMHRII mRNA negative. Thecal and interstitial cells express no detectable AMH mRNA and little or no AMHRII mRNA. The colocalization of AMH and AMHRII mRNAs in granulosa cells of specific follicle types suggests that actions of AMH via AMHRII are autocrine in nature. There is a decreased level of AMH and AMHRII mRNA expression when follicles become atretic. Both mRNA species are eventually lost from atretic follicles, although AMHRII mRNA expression seems to persist somewhat longer than AMH mRNA. During the estrous cycle, no marked changes in the patterns of AMH and AMHRII mRNA expression were detected, except at estrus, when expression of both mRNA species in preantral follicles was decreased compared to that on the other days of the cycle. On postnatal day 5, total ovarian AMH mRNA expression is low and is located in small preantral follicles. During the first weeks of postnatal development, AMH mRNA expression in preantral follicles increases, and the later formed small antral follicles also express AMH mRNA. In contrast, AMHRII mRNA is expressed on postnatal day 5 at a higher level than AMH mRNA, but cannot be localized to specific cell types. From postnatal day 15 onward, AMHRII mRNA expression becomes more restricted to the preantral and small antral follicles. Treatment of prepubertal rats with GnRH antagonist (Org 30276) and human recombinant FSH (Org 32489) or with GnRH antagonist and estradiol benzoate resulted in follicle growth and inhibition of AMH and AMHRII mRNA expression in some, but not all, preantral and small antral follicles. These results indicate that FSH and estrogens may play a role in the down-regulation of AMH and AMHRII mRNA expression in vivo when small antral follicles differentiate into large antral follicles. Furthermore, the FSH surge on the morning of estrus may inhibit AMH and AMHRII mRNA expression in preantral follicles.(ABSTRACT TRUNCATED AT 400 WORDS)

The Persistent Mullerian Duct Syndrome: A Molecular Approach*

A rare form of male pseudohermaphroditism is characterized by the persistence of Müllerian derivatives in phenotypic males. To determine the etiology of this syndrome, we studied the expression of anti-Müllerian hormone (AMH) in six boys, including three brothers, with the persistent Müllerian duct syndrome. All except one presented with an inguinal hernia containing the Müllerian derivatives, and in two boys the hernial sac contained the contralateral testis. AMH was normally expressed in the testicular tissue of two patients, as shown by bioassay of anti-Müllerian activity and immunocytochemistry. The testicular tissue of the other patients had no detectable bioactive or immunoreactive AMH, yet they expressed AMH mRNA with a normal transcription initiation site and in the amount expected for their age. These results prove the heterogeneity of the persistent Müllerian duct syndrome and suggest that it may sometimes involve peripheral insensitivity to AMH.