Dr. Welt is an Assistant Professor at the Harvard Medical School and an Assistant in Medicine at Massachusetts General Hospital. She studies the regulation of normal and abnormal follicular development at all levels of the hypothalamic-pituitary-ovarian axis.

Her work has focused on inhibin, a protein hormone secreted by the granulosa cells of the follicle. The two forms of inhibin, inhibin A and inhibin B, appear to control follicular development both through the negative feedback regulation of FSH and direct autocrine/paracrine effects.

Dr. Welt has been using several clinical models to examine the negative feedback regulation of FSH by inhibin A and inhibin B. Initially, studies of women during normal reproductive aging demonstrated a clear role for both inhibin A and inhibin B in FSH regulation. Currently, selective elimination of estradiol either by blocking action at the receptor level or formation via blockade of aromatase is being used to demonstrate the role of inhibin in FSH control.

Other studies have focused on the regulation of inhibin A and inhibin B secretion by FSH and LH. The two inhibins have distinct patterns of secretion across the menstrual cycle that are not well understood. Using a complimentary in vivo and in vitro approach, inhibin A and inhibin B regulation is being examined both in normal females and in human granulosa cells in culture. This dual approach has elucidated the distinct regulation of inhibin A and inhibin B and has exposed a paradox in inhibin B regulation in vivo and in vitro. These studies have also led to investigation of inhibin's utility as a marker of follicular development during infertility treatment.

In addition, the results from these studies of normal inhibin physiology drive study of the inhibins in abnormal folliculogenesis. Work is in progress to examine the potential consequences of inhibin deficiency in polycystic ovary syndrome, premature ovarian failure, and Fragile X premutations. In addition, previous work by Dr. Welt suggests that activin, a protein structurally related to inhibin but with opposing action, may play a role in ovarian epithelial carcinoma either as a growth factor or a tumor marker. Investigation of inhibin has thus provided insight into normal and abnormal folliculogenesis and the models generated may be used in the study of other growth factors essential to follicular growth and ovulation.

Selected Publications:

• Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, Corrigan EC, Simpson JL, Nelson LM. The FMR1 premutation and reproduction. Fertil Steril. 2007 Mar;87(3):456-65. Epub 2006 Oct 30. Review.

• Cerrato F, Shagoury J, Kralickova M, Dwyer A, Falardeau J, Ozata M, Van Vliet G, Bouloux P, Hall JE, Hayes FY, 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

• Murphy MK, Hall JE, Adams JM, Lee H, Welt CK. Polycystic Ovarian Morphology in Normal Women Does Not Predict the Development of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2006 Aug 1; [Epub ahead of print]  PMID: 16882750

• Page-Wilson G, Smith PC, Welt CK. Prolactin Suppresses GnRH but Not TSH Secretion. Horm Res. 2005 Dec 16;65(1):31-38 [Epub ahead of print]
PMID: 16357488.

• Welt CK, Jimenez Y, Sluss PM, Smith PC, Hall JE. Control of estradiol secretion in reproductive ageing. Hum Reprod. 2006 Aug;21(8):2189-93. Epub 2006 May 9.  PMID: 16684841

• Welt CK, Arason G, Gudmundsson JA, Adams J, Palsdottir H, Gudlaugsdottir G, Ingadottir G, Crowley WF. Defining Constant Versus Variable Phenotypic Features of Women with Polycystic Ovary Syndrome using Different Ethnic Groups and Populations. J Clin Endocrinol Metab. 2006 Aug 29; [Epub ahead of print]  PMID: 16940441

• Welt CK, Gudmundsson JA, Arason G, Adams J, Palsdottir H, Gudlaugsdottir G, Ingadottir G, Crowley WF. Characterizing discrete subsets of polycystic ovary syndrome as defined by the Rotterdam criteria: the impact of weight on phenotype and metabolic features. J Clin Endocrinol Metab. 2006 Dec;91(12):4842-8. Epub 2006 Sep 26. PMID: 17003085

• Welt CK, Hall JE, Adams JM, Taylor AE. Relationship of estradiol and inhibin to the FSH variability in hypergonadotropic hypogonadism or premature ovarian failure. J Clin Endocrinol Metab. 2005; 90: 826-830.

• 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.

• Welt CK, Smith PC, Taylor AE. Evidence of early ovarian aging in fragile X premutation carriers. J Clin Endocrinol Metab. 2004 Sep;89(9):4569-74.

• 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 Sep 2;351(10):959-62.

• Welt CK, Pagan YL, Smith PC, Rado KB, Hall JE. Control of FSH by estradiol and the inhibins: critical role of estradiol at the hypothalamus during the luteal-follicular transition. J Clin Endocrinol Metab. 2003;88:1766-1771.

• Welt CK, Taylor AE, Martin KA, Hall JE. Serum inhibin B in polycystic ovary syndrome: regulation by insulin and LH. J Clin Endocrinol Metab. 2002;87:5559-5565.