Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

Context: The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. Objective: To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Design: Prospective, self-controlled, 3-month clinical trial. Settings: University endocrine clinic. Patients: Men with hypogonadotropic hypogonadism caused by CCPHD. Intervention: Pulsatile GnRH was administered subcutaneously for 3 months. Main outcome measures: Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. Results: A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. Conclusions: This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.

In vivo protective effect of Porphyra yezoensis polysaccharide against carbon tetrachloride induced hepatotoxicity in mice.

To study the protective effect and possible mechanism of Porphyra yezoensis polysaccharide (PYP) in hepatotoxicity mice, acute liver injury was successfully induced by injecting 0.2% carbon tetrachloride (CCl(4)) intraperitoneally. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and liver homogenate, content of malondialdehyde (MDA), activities of total superoxide dismutase (T-SOD) in liver were measured by biochemical methods. Liver index was calculated and pathological changes of the liver tissue were observed microscopically. PYP was found to significantly decrease the activities of ALT and AST (P<0.05), to remarkably lower the liver indexes and MDA level in hepatical tissues in mice (P<0.05), and to upregulated the lower T-SOD level in liver homogenate (P<0.01). Furthermore, histologic examination showed that PYP could attenuate and the extent of necrosis, reduce the immigration of inflammatory cells. PYP plays a protective action against hepatotoxicity induced by CCl(4) in mice, and its mechanisms may be related to free radical scavenging, increasing SOD activities and anti-lipid peroxide.