The challenge of human reproductive studies has been the lack of accurate markers of ovarian function. Therefore, my initial work was in the laboratory focusing on the localization, regulation and endocrine feedback of inhibin A and B, ovarian proteins produced by the granulosa cells. My work demonstrated that inhibin A and B were uniquely regulated and had differing endocrine feedback in relation to each other and compared with estradiol. These studies led to validating inhibin A and B as markers of ovarian follicle number and function. We subsequently demonstrated that inhibin A and inhibin B levels are low in normal aging and abnormal in women carrying the fragile X premutation, and in women with autoimmune oophoritis and polycystic ovary syndrome (PCOS), reflecting the etiology of follicle dysfunction in these disorders.
At the CNS level, my work examined hormone mediators of disruption in normal pulsatile gonadotropin releasing hormone (GnRH) secretion. My work in women with hypothalamic amenorrhea demonstrated that leptin is the primary signal of peripheral energy stores for reproduction. In addition, my laboratory elucidated that prolactin can directly disrupt GnRH secretion, in the absence of dopamine mediation that was previously thought necessary. The prolactin studies led directly to a completed clinical trial examining the safety and efficacy of recombinant prolactin for mothers with lactation insufficiency.
My laboratory is now focused on predicting reproductive disease and its clinical consequences. Therefore, we have performed a genome-wide association study, identifying a locus associated with risk for PCOS. I just received R01 funding from the NICHD to identify the specific risk allele or gene changes resulting in risk for PCOS at that locus.
Welt CK, Smith PC, Taylor AE. Evidence of early ovarian aging in fragile X premutation carriers. J Clin Endocrinol Metab. 2004;89:4569-4574.
Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, Karalis A, Mantzoros CS. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. 2004;351:987-997.
Welt CK, Falorni A, Taylor AE, Martin KA, Hall JE. Selective theca cell dysfunction in autoimmune oophoritis results in multifollicular development, decreased estradiol, and elevated inhibin B levels. J Clin Endocrinol Metab. 2005;90:3069-3076.
Powe CE, Allen M, Puopolo KM, Merewood A, Worden S, Johnson LC, Fleischman A, Welt CK. Recombinant human prolactin for the treatment of lactation insufficiency. Clin Endocrinol (Oxf). 2010;Aug 13, Epub.
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