Lipoamino Acid-Modified GnRH Analogs with Receptor-Mediated Antiproliferative Activity in Prostate and Ovarian Cancer Cells

Gonadotropin-releasing hormone (GnRH) analogs (e.g., triptorelin) are developed to treat hormone-dependent reproductive cancers. However, these analogs lack any significant direct antitumor activity to make them suitable for hormone-refractory reproductive cancers. In this study, we modified GnRH peptide and triptorelin to improve their stability, pharmacokinetic properties, and potency and subsequently broaden their clinical applications in cancer. We investigated biological properties of lipid-modified GnRH analogs, with/without D-amino acid substitution at position 6 to yield GnRH- and triptorelin-based derivatives, respectively, in prostate and ovarian cancer cells. We showed that the improved stability due to lipid-modification and D-amino acid substitution played a pivotal role in enhancing GnRH receptor-mediated direct antiproliferative activity (up to 4.5-fold higher than triptorelin) and gonadotropin-releasing potency. Furthermore, sex steroids played significant but contrasting roles in regulating the direct antiproliferative activity of the lipopeptides in cancer cells. The superior activity of these GnRH analogs over triptorelin renders promises for developing new GnRH receptor ligands to treat hormone-dependent and -refractory cancers, as well as emerging new targeting moieties for the delivery of anticancer agents in GnRH receptor-overexpressing cancers.

Hypothalamic hamartoma presenting as central precocious puberty: a rare case report

Precocious puberty is defined as children attaining puberty more than 2.5 to 3 standard deviations (SD) earlier than the median age, or before the age of eight years in girls and nine years in boys. Hypothalamic hamartoma (HH) are rare, non progressive tumor like malformation. Precocious puberty due to HH occurs particularly at early ages, even 2 or 3 years. Treatment options for isolated CPP due to HH include GnRH analogs agonists continuously stimulates pituitary gonadotrophs, which further help in decreasing and desensitizing the release of LH, and to a lesser extent, FSH till the time puberty naturally set in. We present a case of precocious puberty due to hypothalamic hamartoma in 3 years old girl. Treated with GnRH analog lupirode and responded well to treatment with cessation of menstruation and reduction in breast size.

A Case of Paraphilia with Osteoporosis and Administered with Depot Leuprorelin

Paraphilia is a complex psychological and psychiatric disorder that has been difficult to treat. Leuprorelin has been used as one of the therapeutic methods for paraphilia. Leuprorelin administration could change insulin resistance and accelerate bone loss. The case study in this work was a 59-year-old man who visited a hospital with the chief complaints of frotteuristic behaviors in public places, a continuous increase in sexual desire, and sexual molestation behavior that started in 2007. We injected leuprorelin (3.6 mg) intramuscularly every month for this patient with paraphilia and comorbidities of osteoporosis and hyperthyroidism. The clinical global impression (CGI), Sex Addiction Screening Test (SAST), Wilson Sex Fantasy Questionnaire (WSFQ), physical examination, and laboratory tests were performed. After 12 months of leuprorelin injection for paraphilia, we found a significant improvement in abnormal sexual behavior/desire without aggravation of osteoporosis/hyperthyroidism. Gonadotrophin-Releasing Hormone (GnRH) analogs could be used as alternative or supplementary treatment methods for paraphilia with osteoporosis/hyperthyroidism.