Replacement with GH and levothyroxine appeared to play a crucial role in restoring peripheral reproductive parameters and increasing pituitary hormone expression in Prop1df/df mice.
Key Findings
Results
Treated Prop1df/df mice developed sexual maturation approximately 2 weeks later than wild-type mice.
Male Prop1df/df mice received daily intraperitoneal injections of recombinant human GH and levothyroxine three times weekly beginning at 30 days of age for 60 days.
Sexual maturation timing was compared among three groups: wild-type (Prop+/+), untreated Prop1df/df, and treated Prop1df/df.
The treated Prop1df/df group achieved sexual maturation, but with an approximate 2-week delay compared to wild-type siblings.
Results
GH and levothyroxine replacement induced complete spermatogenesis and increased testicular weight in Prop1df/df mice.
Treated Prop1df/df mice showed an increase in testicular weight relative to untreated Prop1df/df mice.
Complete spermatogenesis was achieved in the treated group.
Untreated Prop1df/df mice did not develop sexual maturation during the study period in most cases.
Results
GH and levothyroxine replacement enhanced LH and FSH expression in the pituitary of Prop1df/df mice.
Treated Prop1df/df mice showed enhanced LH and FSH expression compared to untreated counterparts.
Untreated Prop1df/df mice had low FSH expression.
Pituitary hormone expression levels were among the key reproductive parameters characterized in this study.
Results
Untreated Prop1df/df mice failed to produce offspring and largely did not achieve sexual maturation during the study period.
The untreated Prop1df/df group had no offspring recorded during the study.
Most animals in the untreated group did not develop sexual maturation during the 60-day treatment observation period.
Low FSH expression was observed in untreated Prop1df/df mice, consistent with gonadotropin deficiency due to Prop1 mutation.
Methods
Prop1df/df (Ames dwarf) mice were used as a model of combined GH and thyroid hormone deficiency to study reproductive development.
Ames dwarf mice carry the Prop1df/df mutation, which results in deficiencies of GH, prolactin, and TSH due to pituitary dysfunction.
Animals were started on treatment at 30 days of age, and the treatment duration was 60 days.
Recombinant human GH was administered via daily intraperitoneal injection, and levothyroxine was given three times weekly.
Reproductive anatomy parameters and pituitary hormone expression levels were characterized across the three experimental groups.
Azevedo B, Marques J, Trigueiro N, Yariwake V, Veras M, Tamashiro L, et al.. (2025). Fertility induction associated with improved peripheral reproductive parameters in male Prop1df/df mice subjected to GH and levothyroxine replacement.. Archives of endocrinology and metabolism. https://doi.org/10.20945/2359-4292-2024-0086