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Sex-differences in adrenocortical responsiveness during development in rats
Shintarou Yoshimura1, Shinobu Sakamoto, Hideki Kudo
1Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8510, Japan.
Insights
Neonatal rats show reduced adrenocortical responsiveness to ACTH, with males exhibiting lower responsiveness than females. Sex hormones, particularly testosterone, significantly influence this stress hyporesponsive period (SHRP) in developing 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.
Abstract:
It is known that the stress hyporesponsive period (SHRP), which seems to be related to an immature hypothalamo-pituitary-adrenal (HPA) regulatory system, occurs during the first 2 weeks after birth in rats. In the present study, we investigated the effects of sex-steroid hormones on adrenocortical responsiveness to adrenocorticotropic hormone (ACTH) in neonatal rats. The levels of cyclic adenosine 3',5'-monophosphate (cAMP), corticosterone, and adenylate cyclase activity increased with the dose of ACTH in adrenal cells of males and females in vitro. The ACTH responsiveness in adrenal cells increased with age (7-35 days of age), that is, the loss in responsiveness to ACTH just after birth began to recover in 14-35-day-old rats, but the responsiveness in 14-day-old rats was attenuated in males compared with females. Although castration markedly augmented the responsiveness in male rats, testosterone-replacement in the castrated male rats inhibited the enhancement. Furthermore, the responsiveness in 14-day-intact female rats was suppressed by treatment with testosterone. Expression levels of ACTH receptor mRNA in adrenals increased with age in the female rat, but not in the male. Castration enhanced the level of ACTH receptor mRNA to three-fold of that in intact male rats at 14 days of age, but replacement treatment with testosterone in castrated male rats lowered the elevated levels. Testicular androgens are thought to evoke a gender-specific response in neonates, and the temporal decrease of adrenal ACTH-responsiveness might be due to the topically immature adrenal system as well as the central nervous system in mammals.
