calcimycin and Hypogonadism

The capacity to generate reactive oxygen species (ROS), both basally and after stimulation with the calcium ionophore A23187, was examined in the motile fraction of sperm isolated after swim-up from the semen of 10 naturally fertile men and three groups of infertile patients. The latter included: (1) men with a non-bacterial inflammation of the genital tract (n = 10); (2) men unable to impregnate their partners during an intra-uterine insemination programme (IUI) (n = 8) and their matched controls (n = 6); and (3) men with hypogonadotrophic hypogonadism (HH) who remained infertile after induction of spermatogenesis with gonadotrophin or gonadotrophin-releasing hormone therapy (n = 3) and their matched controls (n = 3). The levels of ROS production were elevated in the sperm of some infertile men with inflammation of the genital tract compared to those found in 10 naturally fertile men. In addition, sperm from those patients who remained infertile after an IUI programme produced higher amounts of ROS compared to their control group who became fertile. Similarly, the production of ROS by sperm from three patients with HH who remained infertile was significantly higher than those of the three men who became fertile. These data suggest that an excessive production of ROS by sperm may explain some cases of idiopathic male infertility.

Topics: Adult; Calcimycin; Cohort Studies; Humans; Hypogonadism; Infertility, Male; Luminol; Male; Oxygen; Prostatitis; Semen; Spermatozoa

The relationship between pituitary GnRH receptors (GnRH-R) and LH responsiveness to GnRH stimulation is not straightforward. In some circumstances, e.g. post-gonadectomy of rats, in lactating rats, during the rat, hamster and monkey oestrous cycles there appears to be a good positive correlation between GnRH-R, basal serum LH values and LH responses to exogenous GnRH. However, in mice following gonadectomy GnRH-R fall by 50% while serum LH levels rise by 10-fold, and in cultured pituitary cells, GnRH exposure increases GnRH-R yet desensitizes cellular responsiveness to subsequent GnRH stimulation. Thus, our original hypothesis that GnRH-R regulation was closely coupled to gonadotroph secretory function does not always hold. Further, we and others, using the rat as an experimental model, hypothesised that the pituitary GnRH receptor content reflected the level of previous pituitary exposure to endogenous GnRH. This view is supported with studies in the GnRH deficient hypogonadotrophic hypogonadal (hpg) mouse in which exogenous GnRH rapidly normalises GnRH-R from very low levels, and is accompanied by rapid activation of pituitary FSH synthesis. However, the post-castration fall in GnRH-R in mice, which is opposite to that in rats, does not appear to be so closely related to endogenous GnRH secretion and cannot be reversed by exogenous GnRH. Using the ovariectomised mouse as an experimental model, evidence has been obtained that estradiol, in addition to GnRH, is essential for maintenance of pituitary GnRH-R in this species. Exogenous estradiol stimulates GnRH-R in OVX mice while it reduces the high values in OVX rats. In female mice estradiol and GnRH have additive stimulatory effects on GnRH-R. Thus, there is species variability in the predominant hormonal regulation of GnRH receptors. In rat pituitary cells in vitro up-regulation of GnRH-R can be effected by several agents which stimulate LH release (GnRH, KCl, DbCAMP) as well as some which do not (Ca ionophore at low concentrations). Receptor up-regulation requires Ca2+ mobilisation and protein synthesis. The data obtained from several in vivo and in vitro model systems supports the conclusion that GnRH receptor changes represent another, medium-term, consequence of GnRH action on the gonadotroph and are not always a locus for the modulation of gonadotrophin secretion and synthesis.

Topics: Animals; Bucladesine; Calcimycin; Calcium; Colforsin; Estrus; Female; Hypogonadism; Lactation; Luteinizing Hormone; Membrane Potentials; Mice; Orchiectomy; Ovariectomy; Potassium; Pregnancy; Receptors, Cell Surface; Receptors, LHRH