Daniel J. Haisenleder, PhD
Graduate School: Wayne State Univ
Primary Appointment: Associate Professor, Medicine, Endocrinology and Metabolism
Regulation of pituitary gene expression.
Email Address: djh2q@Virginia.EDU
Mammalian reproduction requires a series of coordinated actions by the brain (hypothalamus), pituitary [gonadotrope cell that produces and secretes luteinizing hormone (LH) and follicle stimulating hormone (FSH)] and the gonad (ovary and testis). The primary signal from the hypothalamus to the gonadotrope cell is gonadotropin-releasing hormone (GnRH), which is released in a pulsatile manner. Previous studies by our group showed that GnRH pulse pattern could regulate the transcription of LH and FSH subunit genes in a differential manner, with faster frequency stimulating the LH beta gene and slower frequency pulses stimulating FSH beta. Further studies revealed that other gonadotrope-specific genes, that are critical to maintain viable reproductive function (eg. GnRH receptor, follistatin, activin beta B), are also differentially regulated by GnRH pulse frequency.
The theme of our research over the past several years has been to define how GnRH, which binds to a single pituita ry receptor, can regulate several genes within the gonadotrope cell in a divergent manner by altering the pulsatile input signal pattern. Our recent focus has been to determine critical intracellular mechanisms responsible for GnRH-induced regulation of LH, FSH and other gonadotrope-specific genes. We have shown that alterations in intracellular calcium play an essential role in signal transduction of pulsatile GnRH. We also discovered that select intracellular signaling pathways are regulated by GnRH pulse pattern. Current studies are examining potential downstream mediators of GnRH signal transduction, including specific 3rd messenger pathways and transcriptional factors and co-factors.
Estimation of estradiol in mouse serum samples: evaluation of commercial estradiol immunoassays. Haisenleder DJ, Schoenfelder AH, Marcinko ES, Geddis LM, Marshall JC. Endocrinology. 2011 Nov;152(11):4443-7. doi: 10.1210/en.2011-1501. Epub 2011 Sep 20.
GnRH pulse frequency differentially regulates steroidogenic factor 1 (SF1), dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1 (DAX1), and serum response factor (SRF): potential mechanism for GnRH pulse frequency regulation of LH beta transcription in the rat. Burger LL, Haisenleder DJ, Marshall JC. Endocrine. 2011 Jun;39(3):212-9. doi: 10.1007/s12020-011-9440-y. Epub 2011 Mar 16.
Regulation of Lhb and Egr1 gene expression by GNRH pulses in rat pituitaries is both c-Jun N-terminal kinase (JNK)- and extracellular signal-regulated kinase (ERK)-dependent. Burger LL, Haisenleder DJ, Aylor KW, Marshall JC. Biol Reprod. 2009 Dec;81(6):1206-15. doi: 10.1095/biolreprod.109.079426. Epub 2009 Aug 26.
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