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Developmental changes in mullerian inhibiting substance in the cynomolgus monkey, Macaca fascicularis
M M Lee1, M L Gustafson, E Ukiyama
1Pediatric Endocrine Unit, Massachusetts General Hospital, Boston 02114.
Abstract:
Mullerian inhibiting substance (MIS) is a glycoprotein hormone produced in Sertoli cells of the fetal and postnatal testis, and granulosa cells of the pubertal ovary. We examined MIS expression in a nonhuman primate, the cynomolgus macaque monkey (Macaca fascicularis), to define an animal model for studying MIS gene regulation. Changes in testicular MIS mRNA with age were assessed by in situ hybridization of prepubertal to adult testes, Northern analysis of pubertal and adult specimens, and determination of serum MIS concentrations from infancy to adulthood. We found that MIS expression was highest in the youngest animals and decreased progressively with increasing age. Serum MIS concentrations correlated inversely with increasing age (r = -0.74), body weight (r = -0.79), and testicular volume (r = -0.73), but not with testosterone levels (r = -0.35). The mean MIS concentrations +/- SEM for the four developmental age groups were 270.6 +/- 23.8 (infants), 195.5 +/- 18.5 (juveniles), 102.7 +/- 28.4 (peripubertals), and 51.6 +/- 7.1 (adults). This study confirms that nonhuman primate and human MIS are highly homologous and have similar developmental patterns. The normative data for serum MIS concentrations in cynomolgus monkeys at different ages and developmental stages will be invaluable for further work examining MIS regulation.
Insights
Mullerian inhibiting substance (MIS) levels are highest in infant monkeys and decrease with age, mirroring human development. This study establishes the cynomolgus macaque as a valuable model for MIS gene regulation research.
Area of Science:
- Reproductive Biology
- Endocrinology
- Developmental Biology
Background:
- Mullerian inhibiting substance (MIS) is a crucial glycoprotein hormone produced by Sertoli and granulosa cells.
- Understanding MIS gene regulation is vital for reproductive health research.
- Nonhuman primates offer a relevant model for human physiological studies.
Purpose of the Study:
- To investigate Mullerian inhibiting substance (MIS) expression and regulation in the cynomolgus macaque (Macaca fascicularis).
- To establish the cynomolgus macaque as a suitable animal model for studying MIS gene regulation.
- To provide normative data for serum MIS concentrations across different developmental stages in this primate model.
Main Methods:
- In situ hybridization to assess testicular MIS mRNA in prepubertal to adult testes.
- Northern analysis of pubertal and adult testicular specimens.
- Measurement of serum MIS concentrations from infancy to adulthood.
Main Results:
- MIS expression was highest in the youngest cynomolgus monkeys and decreased with age.
- Serum MIS concentrations showed a significant inverse correlation with age (r = -0.74), body weight (r = -0.79), and testicular volume (r = -0.73).
- No significant correlation was observed between serum MIS concentrations and testosterone levels (r = -0.35).
Conclusions:
- MIS exhibits a developmental expression pattern in cynomolgus monkeys that is homologous to humans.
- The cynomolgus macaque serves as an appropriate nonhuman primate model for MIS gene regulation studies.
- Normative serum MIS data across developmental stages in this model are essential for future research.