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Anti-Müllerian hormone: a new actor of sexual dimorphism in pituitary gonadotrope activity before puberty.

Garrel G, Racine C, L'Hôte D, Denoyelle C, Guigon CJ, di Clemente N, Cohen-Tannoudji J - Sci Rep (2016)

Bottom Line: Furthermore, AMH was shown to establish complex interrelations with canonical FSH regulators as it cooperates with activin to induce Fshb expression whereas it reduces BMP2 action.Moreover, AMH specifically regulates FSH and not LH, indicating that AMH is a factor contributing to the differential regulation of gonadotropins.Overall, our study uncovers a new role for AMH in regulating gonadotrope function and suggests that AMH participates in the postnatal elevation of FSH secretion in females.

View Article: PubMed Central - PubMed

Affiliation: Université Paris-Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), F-75013 Paris, France.

ABSTRACT
Anti-Müllerian hormone (AMH) contributes to male sexual differentiation and acts on gonads of both sexes. Identification of AMH receptivity in both pituitary and brain has led to the intriguing idea that AMH participates to the hypothalamic-pituitary control of reproduction, however in vivo experimental evidence is still lacking. We show that AMH stimulates secretion and pituitary gene expression of the gonadotropin FSH in vivo in rats. AMH action is sex-dependent, being restricted to females and occurring before puberty. Accordingly, we report higher levels of pituitary AMH receptor transcripts in immature females. We show that AMH is functionally coupled to the Smad pathway in LβT2 gonadotrope cells and dose-dependently increases Fshb transcript levels. Furthermore, AMH was shown to establish complex interrelations with canonical FSH regulators as it cooperates with activin to induce Fshb expression whereas it reduces BMP2 action. We report that GnRH interferes with AMH by decreasing AMH receptivity in vivo in females. Moreover, AMH specifically regulates FSH and not LH, indicating that AMH is a factor contributing to the differential regulation of gonadotropins. Overall, our study uncovers a new role for AMH in regulating gonadotrope function and suggests that AMH participates in the postnatal elevation of FSH secretion in females.

No MeSH data available.


Related in: MedlinePlus

AMH stimulates FSH secretion and pituitary Fshb expression, in vivo, in female but not in male rats at postnatal day 18.Male and female rats were injected intraperitoneally at pnd 17 with 100 μl of saline solution containing or not 10 μg of AMH precursor (a conventionally used concentration in AMH in vivo studies). Serum LH and FSH secretion (a) and gonadotropin subunits gene expression (b), were determined 18 h after injection. Each value is a mean ± SEM of 13 rats. *P ≤ 0.05; **P ≤ 0.01 compared to control rats.
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f6: AMH stimulates FSH secretion and pituitary Fshb expression, in vivo, in female but not in male rats at postnatal day 18.Male and female rats were injected intraperitoneally at pnd 17 with 100 μl of saline solution containing or not 10 μg of AMH precursor (a conventionally used concentration in AMH in vivo studies). Serum LH and FSH secretion (a) and gonadotropin subunits gene expression (b), were determined 18 h after injection. Each value is a mean ± SEM of 13 rats. *P ≤ 0.05; **P ≤ 0.01 compared to control rats.

Mentions: We next wanted to determine whether AMH could regulate gonadotrope cell activity in vivo. A conventionally used dose of 10 μg of AMH precursor2425 was intraperitoneally (i.p.) injected to pnd 18 rats of both sexes and serum gonadotropins level was measured 18 h later. AMH treatment significantly increased FSH secretion in females (Fig. 6a), identifying AMH as a new regulator of gonadotrope function. Remarkably, AMH effect was restricted to females as no change in FSH secretion was observed in males. Sexual dimorphic expression of pituitary Amhr2 would thus be associated with a differential AMH receptivity between immature male and female rats. Noteworthy, AMH did not affect LH secretion either in males or females (Fig. 6a). Further supporting a role of AMH in the regulation of gonadotrope function, we demonstrated that in vivo AMH treatment increased female pituitary Fshb mRNA (Fig. 6b). Again, this response was sex-dimorphic and restricted to Fshb since AMH did not regulate the expression of Lhb or Cga either in males or in females. Determination of serum steroid levels by gas chromatographic-mass spectrometric analysis did not reveal any significant change in estradiol or testosterone secretion 18 h after AMH administration (estradiol in females: 10 ± 2.8 and 13 ± 2.5 pg/ml; testosterone in males: 0.34 ± 0.13 and 0.23 ± 0.12 ng/ml, before and after AMH treatment respectively, data not shown). AMH thus likely acts directly on pituitary to regulate FSH secretion specifically in females before puberty.


Anti-Müllerian hormone: a new actor of sexual dimorphism in pituitary gonadotrope activity before puberty.

Garrel G, Racine C, L'Hôte D, Denoyelle C, Guigon CJ, di Clemente N, Cohen-Tannoudji J - Sci Rep (2016)

AMH stimulates FSH secretion and pituitary Fshb expression, in vivo, in female but not in male rats at postnatal day 18.Male and female rats were injected intraperitoneally at pnd 17 with 100 μl of saline solution containing or not 10 μg of AMH precursor (a conventionally used concentration in AMH in vivo studies). Serum LH and FSH secretion (a) and gonadotropin subunits gene expression (b), were determined 18 h after injection. Each value is a mean ± SEM of 13 rats. *P ≤ 0.05; **P ≤ 0.01 compared to control rats.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4815011&req=5

f6: AMH stimulates FSH secretion and pituitary Fshb expression, in vivo, in female but not in male rats at postnatal day 18.Male and female rats were injected intraperitoneally at pnd 17 with 100 μl of saline solution containing or not 10 μg of AMH precursor (a conventionally used concentration in AMH in vivo studies). Serum LH and FSH secretion (a) and gonadotropin subunits gene expression (b), were determined 18 h after injection. Each value is a mean ± SEM of 13 rats. *P ≤ 0.05; **P ≤ 0.01 compared to control rats.
Mentions: We next wanted to determine whether AMH could regulate gonadotrope cell activity in vivo. A conventionally used dose of 10 μg of AMH precursor2425 was intraperitoneally (i.p.) injected to pnd 18 rats of both sexes and serum gonadotropins level was measured 18 h later. AMH treatment significantly increased FSH secretion in females (Fig. 6a), identifying AMH as a new regulator of gonadotrope function. Remarkably, AMH effect was restricted to females as no change in FSH secretion was observed in males. Sexual dimorphic expression of pituitary Amhr2 would thus be associated with a differential AMH receptivity between immature male and female rats. Noteworthy, AMH did not affect LH secretion either in males or females (Fig. 6a). Further supporting a role of AMH in the regulation of gonadotrope function, we demonstrated that in vivo AMH treatment increased female pituitary Fshb mRNA (Fig. 6b). Again, this response was sex-dimorphic and restricted to Fshb since AMH did not regulate the expression of Lhb or Cga either in males or in females. Determination of serum steroid levels by gas chromatographic-mass spectrometric analysis did not reveal any significant change in estradiol or testosterone secretion 18 h after AMH administration (estradiol in females: 10 ± 2.8 and 13 ± 2.5 pg/ml; testosterone in males: 0.34 ± 0.13 and 0.23 ± 0.12 ng/ml, before and after AMH treatment respectively, data not shown). AMH thus likely acts directly on pituitary to regulate FSH secretion specifically in females before puberty.

Bottom Line: Furthermore, AMH was shown to establish complex interrelations with canonical FSH regulators as it cooperates with activin to induce Fshb expression whereas it reduces BMP2 action.Moreover, AMH specifically regulates FSH and not LH, indicating that AMH is a factor contributing to the differential regulation of gonadotropins.Overall, our study uncovers a new role for AMH in regulating gonadotrope function and suggests that AMH participates in the postnatal elevation of FSH secretion in females.

View Article: PubMed Central - PubMed

Affiliation: Université Paris-Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), F-75013 Paris, France.

ABSTRACT
Anti-Müllerian hormone (AMH) contributes to male sexual differentiation and acts on gonads of both sexes. Identification of AMH receptivity in both pituitary and brain has led to the intriguing idea that AMH participates to the hypothalamic-pituitary control of reproduction, however in vivo experimental evidence is still lacking. We show that AMH stimulates secretion and pituitary gene expression of the gonadotropin FSH in vivo in rats. AMH action is sex-dependent, being restricted to females and occurring before puberty. Accordingly, we report higher levels of pituitary AMH receptor transcripts in immature females. We show that AMH is functionally coupled to the Smad pathway in LβT2 gonadotrope cells and dose-dependently increases Fshb transcript levels. Furthermore, AMH was shown to establish complex interrelations with canonical FSH regulators as it cooperates with activin to induce Fshb expression whereas it reduces BMP2 action. We report that GnRH interferes with AMH by decreasing AMH receptivity in vivo in females. Moreover, AMH specifically regulates FSH and not LH, indicating that AMH is a factor contributing to the differential regulation of gonadotropins. Overall, our study uncovers a new role for AMH in regulating gonadotrope function and suggests that AMH participates in the postnatal elevation of FSH secretion in females.

No MeSH data available.


Related in: MedlinePlus