The role of catecholamines in the etiology of infertility in diabetes mellitus.

Patients suffering from diabetes mellitus often develop reproductive dysfunction including anovulation, infertility and disrupted pregnancy. The biochemical basis of these phenomena is yet to be provided. The current study utilizes a neuroendocrine paradigm involving an in vitro microdissection technique in conjunction with jugular catheterization to examined the proestrus dynamics of norepinephrine (NE) and the preovulatory luteinizing hormone (LH) surge in streptozotocin (STZ) treated female rats, an animal model for insulin dependent diabetes mellitus. Radioimmunoassays revealed that in control subjects LH was at basal level during the morning of proestrus (900-1200 h); the first significant increase in the level of this pituitary hormone occurred at 1400-1500 h. A maximum peak concentration of LH was attained at 1700 h. In contrast, plasma levels of LH in diabetic subjects showed the first significant increase at 1500 h and peaked at 2000 h. The peak of the LH curve in diabetic rats was reduced by about 65% with a 3 h shift to the right. Alpha-methyl-p-tyrosine-induced blockade of newly synthesized NE-based assay showed that NE turnover rates in several hypothalamic nuclei (e.g. medial preoptic nucleus, MPN; median eminence, ME; suprachiasmatic nucleus, SCN; arcuate nucleus, AN) of control subjects were at basal level during the morning of proestrus (0900-1100 h). However, they increased by the 1200-1400 h interval and remained elevated during the 1500-1700 h. This time dependent increase in hypothalamic NE turnover rates during proestrus was not observed in the STZ diabetic rats. Most of the above metabolic derangements were partially reversed following the institution of insulin replacement therapy. Overall, our data support the concept that the endocrine abnormalities (e.g. infertility, delayed preovulatory LH surge) in diabetes are due, at least in part, to a functional deficit in noradrenergic neurons within the hypothalamus.