Somatotropinoma Infarction During Octreotide Therapy Leading to Bilateral Cavernous Sinus Syndrome

The cyclic somatostatin analog, octreotide, forms the mainstay of medical treatment for acromegaly. In addition to lowering circulating growth hormone levels and shrinking tumor size, octreotide may provide symptomatic relief of headaches associated with growth hormone secreting tumors. The majority of reported complications of octreotide therapy are gastrointestinal and metabolic. The present case illustrates the development of acute bilateral cavernous sinus syndrome with loss of eye movement bilaterally during octreotide therapy. Serial MRI examination suggest tumor infarction as the etiology. The symptoms resolved over 2 months as the tumor shrunk in size and growth hormone was dramatically reduced.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47491/1/11102_2004_Article_324058.pd

Follicle-stimulating hormone signal transduction: Role of carbohydrate in aromatase induction in immature rat Sertoli cells

Receptor activated adenylate cyclase acts as a major transmembrane signalling system. It is widely accepted that upon binding to its receptor, follicle-stimulating hormone (FSH) activates the cAMP-dependent pathway which in turn mediates FSH-induced estradiol production in Sertoli cells. Studies utilizing several chemically derived variants of FSH have demonstrated that these variants bind to the FSH receptors with equal avidity but differ in their ability to activate cAMP-dependent pathways. Since cAMP is believed to be the second messenger responsible for FSH signal transduction, we tested two hypotheses: (1) that the effects of different oFSH variants on cAMP production and aromatase induction (as measured by estradiol production) would be in parallel; and (2) that deglycosylated ovine FSH (DG-oFSH) would antagonize the ability of intact oFSH to stimulate aromatase induction, similar to its reported antagonistic effect on cAMP production.Immature rat (7- to 10-day-old) Sertoli cells were cultured and the effects of several different oFSH variants on cAMP production and/or aromatase induction were tested. The variants tested were native oFSH, DG-oFSH, asialo oFSH (AS-oFSH), a recombinant of intact LH[alpha] and FSH[beta] ([alpha] + [beta]) and a recombinant of deglycosylated LH[alpha] and intact FSH[beta] (DG[alpha] + [beta]). Both native oFSH and [alpha] + [beta] recombinant at relatively large doses (10 ng) elicited a significant increase in extracellular cAMP accumulation as well as total cAMP production. In contrast, DG-oFSH did not produce an increase in cAMP even at 10-fold higher doses than native oFSH. Intracellular cAMP concentrations did not increase following stimulation with native oFSH, DG-oFSH or DG[alpha] + [beta].In contrast to the divergent effects of oFSH and DG-oFSH on cAMP production all variants of oFSH stimulated estradiol production from Sertoli cells albeit with varying potencies. The sensitivity (minimal effective dose) and ED50 (dose at which half maximal response is achieved) of the estradiol (E2) response curve to increasing concentrations of native oFSH were 0.025 +/- 0.01 and 0.33 +/- 0.05 ng, respectively. Asialo-oFSH (AS-oFSH) increased E2 production with a potency (comparative dose required for effect) similar to that of native oFSH. In contrast, there was a 10-fold reduction in potency of DG-oFSH (ED50 of 3.27 +/- 1.7 ng). The efficacy (maximum effect on aromatase induction) of native, DG and AS-oFSH were equipotent. Coincubation of DG-oFSH (0.005-100 ng) with oFSH (0.01-0.625 ng) demonstrated the inductive effects to be additive. In contrast to the reduced potency of DG-oFSH, DG[alpha] -- [beta] recombinants (0.156-160 ng) increased E2 production with a potency similar to that of the native oFSH.Our data suggest: (1) the effects of oFSH variants on cAMP production and aromatase induction are not always parallel; (2) DG-oFSH is a weak agonist and not an antagonist of oFSH-mediated aromatase induction; (3) the reduced potency of DG-oFSH must involve oligosaccharides internal to sialic acid; and (4) depleting the carbohydrate moiety on the [alpha] subunit alone may not be adequate to reduce the potency of oFSH to induce aromatase. Since DG-oFSH does not increase cAMP accumulation, but is able to induce aromatase, the FSH-mediated induction of aromatase may be transduced through other signal pathways. Alternatively, the maximal steroidogenic response may be induced by small, but undetectable, increases in intracellular cAMP concentrations or availability of segregated cAMP pools.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29186/1/0000239.pd