Hormone Helps to Regulate Energy Homeostasis, Neuroendocrine Function, and Metabolism

Leptin is a hormone that plays a central role in fat metabolism. Patients with genetic leptin deficiency are obese, and treatment with leptin leads to dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese people who produce leptin normally are resistant to the weight-loss effects of the hormone. Leptin deficiency is a clinical syndrome associated with distinct conditions such as recent weight loss, diet- or exercise-induced hypothalamic amenorrhea, and lipoatrophy.

Recombinant human leptin is an emerging potential therapy for these leptin-deficient conditions because in replacement doses, it normalizes energy homeostasis, neuroendocrine function, and metabolism.

Replacement of leptin in physiologic doses may help people who have recently lost weight because relative leptin deficiency may drive them to eat more, expend less energy, and regain weight. Leptin also restores ovulatory menstruation in women with hypothalalmic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy.

Scientists have shown that early growth hormone supplementation in rats with growth hormone deficiency can prevent defects in memory developing later in adulthood. The study, published in the Journal of Endocrinology is the first to show that memory defects in adults as a result of growth hormone deficiency arising in childhood can be prevented by growth hormone treatment during adolescence.

Growth hormone levels start off low in early life, and peak just before puberty, after which they gradually decline with increasing age. Growth hormone deficiency can be present from birth, or arise during childhood or adulthood as a result of various disorders. Growth hormone deficiency originating in childhood is treated with growth hormone supplementation to increase body size (mainly height) during adolescence. Until now, it has not been clear if or how this treatment directly affects memory in adulthood, or whether it can prevent learning and memory deficits commonly observed in adults with childhood onset growth hormone deficiency.

Professor Michelle Nicolle and colleagues from Wake Forest University School of Medicine and The Reynolds Oklahoma Center on Aging (University of Oklahoma Health Sciences Center), USA studied rats with a genetic mutation that leads them to produce significantly decreased levels of growth hormone, as a model for early-onset growth hormone deficiency. They assessed the animals’ performance in a water maze test designed to measure spatial memory, at either 8 or 18 months of age. To mimic adult-onset growth hormone deficiency, one group was treated with growth hormone for a specific period during adolescence (4-14 weeks old) only; to mimic childhood-onset growth hormone deficiency, one group was treated with a saline control; and a third group was treated with growth hormone from 4 weeks old throughout their lifespan. The above groups were compared to a control group with normal growth hormone levels.

At 8 months old there was no difference between the groups in performance in the water maze task. However, at 18 months of age, the group with childhood-onset growth hormone deficiency performed significantly poorer in the task than all other groups, indicating poorer spatial learning. This suggests that the growth hormone supplementation during adolescence prevented the age-related deficiencies in learning and memory seen in the childhood-onset group. The group treated with growth hormone during puberty (adult-onset) performed equally well as the group treated with growth hormone into adulthood, indicating no further effect of growth hormone treatment on spatial memory beyond adolescence.

These results show that, in rats, memory impairment in adults as a result of growth hormone deficiency arising in childhood can be reduced or prevented by early growth hormone supplementation. This study highlights the potentially significant role that growth hormone plays in memory function and the importance of further studies with larger sample sizes to determine the mechanisms underlying the effects of growth hormone treatment during adolescence on brain maturation.

Researcher Professor Michelle Nicolle said:

“We carried out this study to investigate the effect of growth hormone supplementation during adolescence on memory function in adults. Our results show that in rats, growth hormone deficiency during adolescence leads to learning and memory deficits in adults. Furthermore, treating growth hormone deficiency by supplementing with growth hormone during puberty prevents this deleterious effect on brain function later in life. This shows that growth hormone replacement during adolescence is important not only for increasing growth but also for brain maturation. This may have important implications for the treatment of patients with growth hormone deficiency and is an aspect of therapy that needs to be taken into account in future clinical growth hormone studies in this key age group.”