Deficiency of somatostatin (SST) receptor type 5 (SSTR5) is associated with sexually dimorphic changes in the expression of SST and SST receptors in brain and pancreas.
The actions of somatostatin (SST) are mediated through five somatostatin receptor subtypes, termed SSTR1-5. Although SSTRs commonly display an overlapping pattern of tissue distribution, subtype-selective responses have been shown to occur in the same tissue. In the present study, we have investigated the changes in SSTR subtypes at the cellular and molecular level in both the brain and the pancreatic islets of mice deficient in SSTR5 (SSTR5KO). Expression levels of insulin and glucagon were also determined in the pancreas of these mice. Semi-quantitative RT-PCR and Western blot analysis showed significant increases in the expression of SSTR2 and 3 with a corresponding reduction in SSTR4 in the brains of female SSTR5KOs, while no changes were observed in male KOs. Strikingly, SST mRNA and SST-like immunoreactivity (SST-LI) were reduced in the brain of male KO animals but not in their female counterparts. In male SSTR5KO islets, there was an increase in the number of cells immunoreactive for SSTR1-3, whereas in female islets only SSTR3 expression was increased. Pancreatic SST-LI and SST mRNA, as well as immunoreactivity for insulin were reduced in male but not in female KO mice. These data indicate that deficiency of SSTR5 leads to subtype-selective sexually dimorphic changes in the expression of both brain and pancreatic SSTRs.
Ramírez
José L
JL
Fraser Laboratories, Departments of Medicine, Royal Victoria Hospital, McGill University, Montreal, Que., Canada H3A 1A1.
Grant
M
M
Norman
M
M
Wang
X P
XP
Moldovan
S
S
de Mayo
F J
FJ
Brunicardi
C
C
Kumar
U
U
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D001923:Brain Chemistry; D005260:Female; D005934:Glucagon / Q000032:analysis; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D010179:Pancreas / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D012727:Sex Characteristics; D013004:Somatostatin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; C094573:somatostatin receptor 5; D005934:Glucagon