Gonadotrophic control of human granulosa cell glycolysis

Abstract

Follicular fluid lactate levels were measured in women undergoing infertility surgery during the follicular phase or oocyte recovery for in-vitro fertilization (IVF). In the largest ovulatory follicle lactate levels were low in the mid-follicular phase (group 1), 1.6-fold higher just prior to the onset of the luteinizing hormone (LH) surge (group 2) and a further 2.5-fold higher after the onset of the LH surge (group 3). In IVF patients mean lactate levels in all aspirated follicles were similar to those in group 3 subjects, but the levels within each patient were variable and were positively correlated with follicular volume. Basal granulosa cell lactate accumulation in vitro was 3-fold higher in group 3 compared with group 2 subjects, but stimulation by FSH or HCG was higher in group 2 (2- to 3-fold) compared with group 3 (1.4- to 2-fold). These results demonstrate that human follicular fluid lactate levels increase as a function of the maturity and size of the developing follicle. Granulosa cell lactate accumulation in vitro is under gonadotrophic control, which suggests that the effects observed in vivo reflect changes in granulosa cell glycolysis in response to gonadotrophic stimulation. Our findings support the concept that low molecular weight energy metabolites transduce gonadotrophin signals that regulate oocyte maturation.

Characterization of ovarian follicular fluids of sheep, pigs and cows using proton nuclear magnetic resonance spectroscopy

“…Although more sensitive methods will be required to determine whether subtle differences exist (particularly in the sparse interstitial fluids of the follicle epithelium and cumulus oophorus), it appears reasonable to predict that the concentrations of sugars, amino acids and fatty acids in follicular fluid are indicated by those of the blood perfusing the ovary. Exceptions to the generalisation exist beside steroids, which have remarkably high concentrations in follicular fluid 1, 2, t 3 Concentrations of lactate exceed those of blood; evidently it accumulates during follicular growth under the control of gonadotrophins and provides an important source of energy for the oocyte 14 The results appear to be in conflict with chemical analysis of porcine follicular fluids in which hypoxanthine concentrations were estimated to be 1-2 mmoll-1 by other methods 15. At comparable concentrations in vitro, this base inhibits meiotic maturation of mouse oocytes, but the present results indicated that physiological concentrations in 3 species are much lower.…”

Mitochondrial 3 beta-hydroxysteroid dehydrogenase (HSD) is essential for the synthesis of progesterone by corpora lutea: An hypothesis

“…As follicular size increases, lactate levels also increase [66], coinciding with the start of antrum formation and detectable estradiol-17β secretion [66,67]. After the LH surge, the levels of lactate increase an additional 2.5 fold [66,68]. In luteal tissue, a high percentage of the glucose taken up is metabolized only as far as pyruvate and lactate [69].…”

The effect of metformin treatment in vivo on acute and long-term energy metabolism and progesterone production in vitro by granulosa cells from women with polycystic ovary syndrome

“…Glucose, metabolized under anoxic conditions to lactate, was shown to be the preferred energy substrate required to support the gonadotrophin-induced differentiation of sheep GCs in vitro ; fructose and pyruvate, but not galactose, were consumed as alternative sources of energy. In normal human ovaries, it is established that the GCs metabolize glucose by glycolysis and this results in the production of lactate and pyruvate (Billig et al , 1983; Harlow et al , 1987; Boland et al , 1993). While the pyruvate so derived is utilized by the oocytes as their energy source, lactate either diffuses into the blood or is converted back to pyruvate (Leese and Lenton, 1990; Boland et al , 1994).…”