Somatostatin is one of the numerous peptides described in the Harderian gland of different animals. With the aim of trying to elucidate its physiological role, we investigated whether this peptide is expressed in OFA rat Harderian gland at different ages and seasons and, if so, studied the regulatory proteins involved in the activation of the somatostatin gene, and also whether it contains any somatostatin receptors. Nursing (4-15-day-old), prepubertal (21-30-dayold), and adult (54-day-old) OFA rats were sacrificed by decapitation throughout the year, and the Harderian glands were excised and immediately frozen in liquid N2. The expression of somatostatin and its receptors was investigated using RT-PCR techniques; additionally, the existence of proteins which bind to cAMP responsive elements (CRE) was investigated using a band-shift technique. The somatostatin gene was expressed in the Harderian gland of rats aged 4-30 days in autumn and winter but not in spring or summer or in older animals. However, the somatostatin receptor was expressed throughout the year at all the ages studied. In the autumn, nuclear proteins binding to CRE (CREB) were present in 8-10-day-old rats but not in younger 4-day-old animals. We conclude that rat Harderian gland cells transcribe the somatostatin gene depending on the season and age of the animals, while its receptor is always present at all the ages studied; the CREB found produces the same retardation complex as ICER (inducible CAMP early repressor), an isoform of CREM (CAMP responsive element modulator), which in the pineal has been shown to be under adrenergic control. Since somatostatin expression is regulated by CAMP mechanisms, it is feasible that the existence of this repressor ICER could explain why somatostatin expression disappears in adult animals once maturation is complete. CREB, CREM, ICER (inducible cAMP early repressor) o 1996 Wiley-Liss, Inc.