Dr. Welt is an Assistant Professor at the Harvard Medical School and an Assistant in Medicine at Massachusetts General Hospital. Dr. Welt 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:

• Welt C, Martin KA, Taylor AE, Lambert-Messerlian GM, Crowley Jr WF, Smith JA, Schoenfeld DA, Hall JE. Frequency modulation of FSH during the luteal-follicular transition: evidence for FSH control of inhibin B in normal women. J Clin Endocrinol Metab. 1997;82:2645-2652.

• Welt C, Lambert-Messerlian GL, Zheng W, Crowley Jr WF, Schneyer AL. The presence of activin, inhibin and follistatin in epithelial ovarian carcinoma. J Clin Endocrinol Metab 1997;82:3720-3727.

• Welt CK, McNicholl DJ, Taylor AE, Hall JE. Female reproductive aging is marked by decreased secretion of dimeric inhibin. J Clin Endocrinol Metab 1999;84:105-111.

• Welt CK, Schneyer AL. Differential regulation of inhibin B and inhibin A by FSH and local growth factors in human granulosa cells from small antral follicles. J Clin Endocrinol Metab. 2001; 86:330-336.

• Welt CK, Smith ZA, Pauler DK, Hall JE. Differential regulation of inhibin A and inhibin B by LH, FSH and stage of follicle development. 2001; 86:2531-2537.

• 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.

• 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, 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, Hall JE, Adams JM, Taylor AE. Relationship of estradiol and inhibin to the FSH variability in premature ovarian failure. 2004 J Clin Endocrinol Metab (in press).