The release and synthesis of growth hormone (GH) from somatotrophs located within the anterior pituitary gland is stimulated by GH releasing hormone (GHRH) and inhibited by somatostatin (SRIF) from corresponding neurons in the hypothalamus. We previously characterized the age-associated decline in pulsatile GH secretion in mice, and observed a rapid decline in total and pulsatile GH secretion between 12 and 16 weeks of age. While it has been suggested that the age-associated decline in GH secretion may be a consequence of reduced GHRH cell numbers (and consequently GH secretion), it remains unclear whether SRIF contributes to this change.
Using in situ hybridisation and morphometric methods, we mapped the distribution of SRIF within the mouse brain at 4, 8 and 16 weeks of age. These ages correspond to early pubertal, early adulthood and adulthood, respectively. Given that SRIF inhibits the secretion of GH, we anticipated that age-associated changes in pulsatile GH secretion might occur in conjunction with age-related changes in the level of hypothalamic SRIF expression. Consistent with previous observations in rats, SRIF perikarya are located along the rostro-caudal extent of the periventricular nucleus (PeV), arcuate nucleus (ARC) and other hypothalamic regions including suprachiasmatic, ventromedial (VMH) and dorsomedial (DMH) nuclei. Additional measures combining retrograde tracing (intraperitoneal fluorogold injection) further clarify the neuroendocrine mechanisms of SRIF in regulating GH secretion within the ARC specific to the mouse. Expression patterns of SRIF in early pubertal, early adult and adult mice clarify the potential role of SRIF in regulating GH secretion in the mouse, and provide new insights regarding the role of somatostatin in regulating age-associated changes in pulsatile GH secretion.
This work was supported by The Australian National Health and Medical Research Council and The University of Queensland. Hwee Yim Angeline Tan is a recipient of the International Postgraduate Research Scholarship.