Control of gonadal function by the pituitary gonadotropins is firmly established. However, the role of luteinizing hormone (LH) heterogeneity and its clinical ramifications are poorly understood. The overall objective of the proposed research is to investigate WHAT CAUSES LH HETEROGENEITY, the QUANTITATION AND REGULATION OF LH HETEROGENEITY and the BIOLOGICAL FUNCTIONS OF LH HETEROGENEITY. At present, the molecular basis for LH heterogeneity is not fully understood. Our preliminary studies suggest that the multiple charge isomers of both human (h) and ovine (o) LH are associated with their oligosaccharides. Thus, we propose to examine the fine structures of the various sugar units attached to LH and relate oligosaccharide structures to the distinct molecular forms of LH observed in pituitary extracts. Previous studies suggested a critical role for oligosaccharides in the expression of LH biological activity (LH deglycosylated with hydrogen fluoride). Our preliminary data using a less radical method (endoglycosidase F) suggest otherwise. To address this disparity and to carefully dissect the role of carbohydrate in LH action we propose to examine circulatory survival and the abilities of each naturally occurring oLH and hLH isohormone to bind to receptors and to stimulate the production of cAMP and testosterone. LH in which specific components of the oligosaccharides have been removed will be similarly examined. We propose to continue identifying and quantitating the molecular forms of LH """"""""isohormones"""""""") in the pituitary using sheep subjected to various endocrine manipulations and to establish their relationship with forms which are secreted. These experiments will illustrate changes in LH heterogeneity under various endocrine conditions and possibly reveal the factors which modulate the LH isohormone profile. In order to identify and characterize molecular forms of LH which are immunoreactive but possess little biological activity we propose examining LH isohormones found in serum and urine of humans with normal and abnormal reproductive function as well as changes associated with the onset and quiescence of gonadal function. These studies should clarify the role of specific molecular forms of LH in the regulation of gonadal function.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD018879-04A2
Application #
3316043
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1983-09-01
Project End
1991-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Nebraska Lincoln
Department
Type
Earth Sciences/Resources
DUNS #
555456995
City
Lincoln
State
NE
Country
United States
Zip Code
68588
Christianson, S L; Zalesky, D D; Grotjan, H E (1998) Ovine luteinizing hormone heterogeneity: androgens increase the percentage of less basic isohormones. Domest Anim Endocrinol 15:87-92
Kirkpatrick, B L; Grotjan, H E (1998) Neither castration nor steroid-replacement change the apparent molecular size of FSH in the sheep pituitary. Anim Reprod Sci 49:239-46
Keel, B A; Zalesky, D D; Sohaili, I et al. (1994) Heterogeneity of gonadotropins and levels of uncombined luteinizing hormone subunits in pituitaries of cryptorchid rams. J Androl 15:29-35
Zalesky, D D; Schanbacher, B D; Grotjan, H E (1993) Effect of immunization against LHRH on isoforms of LH in the ovine pituitary. J Reprod Fertil 99:231-5
Zalesky, D D; Nett, T M; Grotjan, H E (1992) Ovine luteinizing hormone: isoforms in the pituitary during the follicular and luteal phases of the estrous cycle and during anestrus. J Anim Sci 70:3851-6
Stumpf, T T; Wolfe, M W; Roberson, M S et al. (1992) Bovine luteinizing hormone (LH) isoforms and amounts of messenger ribonucleic acid for alpha- and LH beta-subunits in pituitaries of cows immunized against LH-releasing hormone. Biol Reprod 47:776-81
Stumpf, T T; Roberson, M S; Wolfe, M W et al. (1992) A similar distribution of gonadotropin isohormones is maintained in the pituitary throughout sexual maturation in the heifer. Biol Reprod 46:442-50
Hejl, K M; Wolfe, M W; Kinder, J E et al. (1992) Bioactive and immunoreactive concentrations of circulating luteinizing hormone during sexual maturation in the bovine. Biol Reprod 46:1205-10
Zalesky, D D; Grotjan, H E (1991) Comparison of intracellular and secreted isoforms of bovine and ovine luteinizing hormone. Biol Reprod 44:1016-24
Zalesky, D D; Grotjan, H E (1991) Luteinizing hormone in the bovine pars tuberalis: secretion in response to luteinizing hormone releasing hormone and intracellular isoforms. Domest Anim Endocrinol 8:179-87

Showing the most recent 10 out of 22 publications