The number of lactotrophs is reduced in the anterior pituitary of streptozotocin-induced diabetic rats.
OBJECTIVE
Prolactin secretion is often reduced in insulin dependent diabetes mellitus, but little is known about the mechanism involved. Since changes in the hormonal environment modulate cell proliferation, death and cellular makeup of the anterior pituitary, we have analysed whether the number of lactotrophs is reduced in diabetic rats.


METHODS
Streptozotocin induced diabetic rats were maintained hyperglycaemic for 2 months. Pituitary prolactin, growth hormone, Bcl-2, Bax and PCNA concentrations were analysed by western blot analysis. In situ hybridisation was used for quantification of prolactin and growth hormone mRNA containing cells. Cell death was detected by TUNEL labelling, alone and in combination with immunocytochemistry for prolactin or growth hormone.


RESULTS
Diabetic rats had fewer lactotrophs ( p<0.01). This was coincident with a decrease in overall protein and prolactin content. An increase in pituitary cell death was found and some of the TUNEL labelling co-localised with prolactin immunostaining. No change in the concentration of Bcl-2 or Bax, proteins implicated in apoptosis, was detected. PCNA content was higher in the pituitaries of diabetic rats, suggesting increased proliferation.


CONCLUSIONS
Anterior pituitary cell turnover is affected in poorly controlled diabetes mellitus. A decrease in the number of lactotrophs, as a result of increased cell death, could underlie, at least in part, the reduction in prolactin secretion observed in diabetic animals.
Arroba
A I
AI
Unit of Investigation, Department of Endocrinology, University Hospital Niño Jesús, Avenida Menéndez Pelayo, 65, 28009 Madrid, Spain.
Frago
L M
LM
Pañeda
C
C
Argente
J
J
Chowen
J A
JA
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011388:Prolactin; D013006:Growth Hormone