Sex-differences in adrenocortical responsiveness during development in rats

Area of Science:

• Endocrinology
• Neuroscience
• Developmental Biology

Background:

• The stress hyporesponsive period (SHRP) in neonatal rats is linked to an immature hypothalamo-pituitary-adrenal (HPA) system.
• Adrenocortical responsiveness to adrenocorticotropic hormone (ACTH) is diminished during early postnatal life.

Purpose of the Study:

• To investigate the impact of sex-steroid hormones on adrenocortical responsiveness to ACTH in neonatal rats.
• To explore the age-related recovery of HPA axis function and its sexual dimorphism.

Main Methods:

• In vitro analysis of adrenal cells from neonatal rats (7-35 days old) exposed to varying doses of ACTH.
• Measurement of cyclic adenosine 3',5'-monophosphate (cAMP), corticosterone, and adenylate cyclase activity.
• Assessment of ACTH receptor mRNA expression levels in adrenal glands following hormonal manipulation (castration and testosterone replacement).

Main Results:

• ACTH responsiveness in adrenal cells increased with age, with recovery beginning around 14 days.
• Male rats at 14 days showed attenuated ACTH responsiveness compared to females.
• Castration in males enhanced responsiveness, while testosterone replacement inhibited this enhancement. Testosterone also suppressed responsiveness in females.
• ACTH receptor mRNA levels increased with age in females but not males; castration elevated these levels in males, an effect reversed by testosterone.

Conclusions:

• Testicular androgens induce gender-specific responses in neonatal rats.
• The temporary decrease in adrenal ACTH responsiveness during SHRP may stem from immature adrenal and central nervous systems.
• Sex hormones play a critical role in modulating the HPA axis maturation and recovery from the SHRP.