Biomedical subjects

Linda F Adams

Publications and source records attributed to Linda F Adams.

3 recordsLinked to original sources

PubMed2004

Prostaglandin synthases: recent developments and a novel hypothesis.

Cells are continuously exposed to cues, which signal cell survival or death. Fine-tuning of these conflicting signals is essential for tissue development and homeostasis, and defective pathways are linked to many disease processes, especially cancer. It is well established that prostaglandins (PGs), as signalling molecules, are important regulators of cell proliferation, differentiation and apoptosis. PG production has been a focus of many researchers interested in the mechanisms of parturition. Previously, investigators have focussed on the committed step of PG biosynthesis, the conversion by prostaglandin H synthase (PGHS; also termed cyclo-oxygenase, COX) of arachidonic acid (AA) (substrate) to PGH2, the common precursor for biosynthesis of the various prostanoids. However, recently the genes encoding the terminal synthase enzymes involved in converting PGH2 to each of the bioactive PGs, including the major uterotonic PGs, PGE2 (PGE synthase) and PGF2alpha (PGF synthase), have been cloned and characterized. This review highlights how the regulation of the expression and balance of key enzymes can produce, from a single precursor, prostanoids with varied and often opposing effects.

Arachidonic Acid↗

PubMed2003

Abnormal luteal phase excitability of the motor cortex in women with premenstrual syndrome.

BACKGROUND: Premenstrual syndrome (PMS) involves an aberrant behavioral response to normal hormone secretion. Pathogenetic theories posit abnormal modulation of gamma-aminobutyric acid (GABA) transmission in the brain by neuroactive metabolites of progesterone (neurosteroids). In earlier transcranial magnetic stimulation (TMS) studies of the motor cortex, we showed that inhibition increases in the luteal phase, consistent with neurosteroid action at the GABA(A) receptor. Here, we studied women with PMS to see if their response to endogenous progesterone differed from that of control subjects. METHODS: We studied nine women with PMS and 14 control subjects during the midfollicular and luteal phases with paired TMS. Subthreshold conditioning TMS was followed by test stimulation that produced a motor evoked potential (MEP) in a hand muscle. We gave pairs at each of seven intervals (2-10 msec) and unconditioned stimuli, measuring the amplitude ratio of the average MEP from the pairs at each interval to that from the unconditioned stimuli (ratio < 1 = inhibition). RESULTS: Both groups showed the same follicular phase response to paired TMS. Control subjects showed more inhibition in the luteal phase. Women with PMS showed relative facilitation. CONCLUSIONS: This is the first physiological evidence for an abnormal brain response to progesterone in PMS.

Adult↗

PubMed2002

Effects of ovarian hormones on human cortical excitability.

Ovarian steroids appear to alter neuronal function in women, but direct physiological evidence is lacking. In animals, estradiol enhances excitatory neurotransmission. Progesterone-derived neurosteroids increase GABAergic inhibition. The effect of weak transcranial magnetic stimulation of the motor cortex on the motor evoked potential (MEP) from transcranial magnetic stimulation given milliseconds later is changed by GABAergic and glutamatergic agents. Using this technique previously, we showed more inhibition in the luteal phase relative to the midfollicular menstrual phase, which is consistent with a progesterone effect. To detect the effects of estradiol, we have now divided the follicular phase. We tested 14 healthy women during the early follicular (low estradiol, low progesterone), late follicular (high estradiol, low progesterone), and luteal (high estradiol, high progesterone) phases, with interstimulus intervals from 2 to 10msec (10 trials at each interval and 40 unconditioned trials). We calculated the ratio of the conditioned MEP at each interval to the mean unconditioned MEP: the higher the ratio, the less inhibition and the more facilitation caused by the first stimulus. The combined ratios increased significantly from the early follicular phase to the late follicular phase and then decreased again in the luteal phase. These findings demonstrate an excitatory neuronal effect associated with estradiol and confirm our earlier finding of inhibition associated with progesterone.

Adult↗