Ascorbic acid stimulates gonadotropin release by autocrine action by means of NO

Abstract

Because high concentrations of ascorbic acid (AA) are found in the adenohypophysis, we hypothesized that it might have an acute effect on the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the gland, particularly because we have reported that AA rapidly inhibits stimulated LH-releasing hormone (LHRH) release from medial basal hypothalamic explants. Incubation of anterior pituitary halves from adult male rats with graded concentrations of AA for 1 h induced highly significant release of both FSH and LH with a minimal effective concentration of 10 ؊5 M. Release remained on a plateau from 10 ؊5 to 10 ؊2 M. When both AA and an effective concentration of LHRH were incubated together, there was no additive response to LHRH and the response was the same as to either compound alone. The FSH and LH release in response to AA was blocked by incubation with N G -monomethyl-L-arginine (NMMA) (300 M), a competitive inhibitor of NO synthase. NMMA also inhibited LHRH-induced LH and FSH release and gonadotropin release in the presence of both LHRH and AA, whereas sodium nitroprusside, a releaser of NO, stimulated LH and FSH release. Membrane depolarization caused by incubation in high potassium (K ؉ ‫؍‬ 28 or 56 mM) medium stimulated release of FSH, LH, and AA that was blocked by NMMA. We hypothesize that AA is released with FSH and LH from secretory granules. AA is transported back into gonadotropes by the AA transporter and increases intracellular [Ca 2؉ ]-activating NO synthase that evokes exocytosis of gonadotropins and AA by cGMP .anterior pituitary gland ͉ follicle-stimulating hormone ͉ luteinizing hormone ͉ N G -monomethyl-L-arginine ͉ sodium nitroprusside A scorbic acid (AA) is a six-carbon ketolactone-synthesized from glucose (1, 2). It is an essential vitamin for humans, primates, guinea pigs, and bats, as they lack L-gulono-␥-lactone oxidase, the last enzyme involved in its synthesis from glucose (1, 3). AA is abundant in many endocrine tissues (4, 5) and plays a pivotal role in the control of adrenal and gonadal steroidogenesis (6). Several tissues in the body accumulate AA and its biologically active oxidized form, dehydroascorbic acid. The anterior pituitary gland, brain, adrenal gland, and gonads have high concentrations of AA (2, 7-10). The concentration of AA in the brain ranges between 1.1 and 1.7 mM and remains constant despite variation in AA ingestion (11,12). Intracellular AA concentration is much higher than extracellular AA concentration, and changes in neuronal activity were shown to have a profound influence on extracellular AA (13-18). AA is further concentrated in isolated nerve terminals, and synaptic vesicles concentrate AA by an active transport mechanism (19,20).Previously, we evaluated the effect of AA on basal and stimulated release of luteinizing hormone (LH)-releasing hormone (LHRH) from medial basal hypothalamic explants produced by high potassium medium and N-methyl-D-aspartic acid (NMDA). Sodium nitroprusside (NP), which spontaneously releases NO-stimulate...

The Role of Coconut Water on Nicotine-Induced Reproductive Dysfunction in Experimental Male Rat Model

“…In addition, coconut water is proven to improve the serum cholesterol levels in rats [8]. Nitric oxide formed from L-arginine by the enzyme NOS and ascorbic acid, stimulates the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary gland and increased the level of androgens [33]. Calcium, magnesium proves to have essential role in spermatogenesis and fertility [34].…”

Oxidative Stress in Nonobese Women with Polycystic Ovary Syndrome: Correlations with Endocrine and Screening Parameters

“…High concentrations of antioxidants are found in the adenohypophysis [61][62][63] . It has been reported [62] that antioxidants may stimulate the gonadotropin secretion that activates the release of LH from the gland.…”

“…It has been reported [62] that antioxidants may stimulate the gonadotropin secretion that activates the release of LH from the gland. Vitamin E releases LH-RH from the hypothalamus and LH from the pituitary [63] .…”

Effect of some antioxidants on the reproductive performance in rats

“…In this concern, Miller and Cicero, (1986) found that AA has the ability to increase LHRH in vitro from hypothalamic fragments. Moreover, in vitro research of Karanth et al, (2001) showed that incubation of anterior pituitary from adult male rats with AA for one hour induced significantly high release of both FSH and LH. Regarding taurine, Sloley et al, (1992) documented that injection of goldfish with taurine caused an elevation in serum gonadotropin concentrations.…”