Dr. Stephanie Seminara is a faculty member of the Reproductive Endocrine Unit at Massachusetts General Hospital, an Assistant Professor of Medicine at Harvard Medical School, and an Assistant in Medicine at Massachusetts General Hospital.
She is also Co-Director of the Reproductive Endocrine Associates, the clinic practice of the Reproductive Endocrine Unit. In the clinic, she sees both men and women with a broad variety of reproductive abnormalities, and has a particular interest in men and women with hypogonadal states.
Dr. Seminara studies the genetics of idiopathic hypogonadotropic hypogonadism, a disease characterized by delay of pubertal development and infertility.
The broad goal of Dr. Seminara's work is the elucidation of the genes that cause congenital, idiopathic hypogonadotropic hypogonadism (gonadotropin releasing hormone [GnRH] deficiency) and the exploration of genotype/phenotype correlations for patients with this disorder. Identification of the genes that modify GnRH secretion is critical to advance the understanding of normal reproduction. Human “knock out” models of isolated GnRH deficiency represent a unique biologic opportunity to identify the gene(s) relevant to GnRH secretion.
To date, the genetics of idiopathic hypogonadotropic hypogonadism (IHH) has been challenging to elucidate, as this condition is characterized by rich clinical and genetic heterogeneity, variable modes of inheritance, and association with other anomalies. Selected genetic approaches have highlighted the fact that children of marriages between related individuals heterozygous at a given genetic locus have a high probability of being affected due to homozygosity by descent. Dr. Seminara and colleagues have used linkage analysis in a large consanguineous family with IHH. Their work has uncovered that mutations in a G protein coupled receptor, GPR54, are a cause of autosomal recessive IHH. Thus, GPR54, and its ligand, metastin, are critical regulators of the reproductive axis. Further genetic studies are underway to elucidate the role of these proteins.
• Lapatto R, Pallais JC, Zhang D, Chan YM, Mahan A, Cerrato F, Le WW, Hoffman GE, Seminara SB. Kiss1 / mice exhibit more variable hypogonadism than gpr54 / mice.
Endocrinology. 2007 Oct;148(10):4927-36. Epub 2007 Jun 26.
• Cerrato F, Seminara SB. Human genetics of GPR54. Rev Endocr Metab Disord. 2007 Mar;8(1):47-55. PMID: 17334928
• Ramaswamy S, Seminara SB, Pohl CRT, Dipietro MJ, Crowley WF Jr, Plant TM. Effect of continuous iv administration of human metastin 45-54 on the neuroendocrine activity of the hypothalamic-pituitary-testicular axis in the adult male rhesus monkey (Macaca mulatta). Endocrinology. 2007 Apr 5; [Epub ahead of print] PMID: 17412800
• Cerrato F, Shagoury J, Kralickova M, Dwyer A, Falardeau J, Ozata M, Van Vliet G, Bouloux P, Hall JE, Hayes FJ, Pitteloud N, Martin KA, Welt C, Seminara SB. Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism. Eur J Endocrinol. 2006 Nov;155 Suppl 1:S3-S10. PMID: 17074994
• Corssmit EP, Seminara SB, Pitteloud N, Fliers E. Kallmann syndrome in a 47,XXX patient. Am J Med Genet A. 2005 Nov 15;139A(1):52-53. PMID: 16222664
• Pallais JC, Bo-Abbas Y, Pitteloud N, Crowley WF Jr, Seminara SB. Neuroendocrine, gonadal, placental, and obstetric phenotypes in patients with IHH and mutations in the G-protein coupled receptor, GPR54. Mol Cell Endocrinol. 2006 Jul 25;254-255:70-7. Epub 2006 Jun 6. PMID: 16757106
• Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF Jr, Plant TM. Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications. Endocrinology. 2006 May;147(5):2122-6. Epub 2006 Feb 9. PMID: 16469799
• Seminara, SB. Mechanisms of Disease: the first kiss-a crucial role for kisspeptin-1 and its receptor, G-protein-coupled receptor 54, in puberty and reproduction. Nat Clin Pract Endocrinol Metab. 2006 Jun;2(6):328-34. PMID: 16932310
• Seminara SB. We all remember our first kiss: kisspeptin and the male gonadal axis.
J Clin Endocrinol Metab. 2005 Dec;90(12):6738-40. No abstract available.
• Miura K, Acierno JS Jr, Seminara SB. Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH). J Hum Genet. 2004 Apr 15 [Epub ahead of print]
• Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O'Rahilly S, Carlton MB, Crowley WF Jr, Aparicio SA, Colledge WH. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003 Oct 23;349(17):1614-27.
• Bo-Abbas Y, Acierno jr JS, Shagoury JK, Crowley Jr WF, Seminara SB. Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the GnRH and GnRH receptor genes. J Clin Endocrinol Metab. 2003: 88:2730-2737. • Acierno jr JS, Shagoury JK, Bo-Abbas Y, Crowley Jr WF, Seminara SB. A locus for autosomal recessive idiopathic hypogonadotropic hypogonadism on chromosome 19p13.3. J Clin Endocrinol Metab. 2003: 88:2947-2950.
• Oliveira LMB, Seminara SB, Beranova, Hayes FJ, Valkenburgh SB, Costa EMF, Schipani E, Latronico AC, Crowley Jr WF, Vallejo M. Novel mutations of the KAL gene in hypogonadotropic hypogonadism: neuroendocrine characteristics, modes of inheritance, and genotype-phentoype correlations. J Clin Endocrinol Metab. 2001; 86:1532-1538
• Beranova M, Oliveira LMB, Bedecarrats G, Schipani E, Vallejo M, Ammini P, Quintos JB, Hall JE, Martin KA, Hayes FJ, Pittleloud N, Kaiser U, Crowley Jr WF, Seminara SB. Incidence, spectrum, and modes of inheritance of GnRH receptor mutations in idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2001; 86:1580-1588.