Date of Award

1989

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

Treatment in utero with busulfan or irradiation, resulted in adult rats with decreased serum androgen and increase serum lutenizing hormone (LH). Leydig cells (LC) from lesioned rats had increased in vitro androgen production (AP) and increased hCG binding per LC. Serum androgen was decreased, yet AP per LC was increased. Possibly, spermatogenic disruption resulted in gonads with decreased number of LC which had increased LH responsiveness.;To distinguish whether the effects of spermatogenic disruption on LC were due to local or systemic modulation, disruption of spermatogenesis by efferent duct ligation or cryptorchidism was done as unilateral or bilateral treatments. LH stimulated AP per LC from lesioned testes was greater than control. Decreased serum androgen and elevated serum LH occurred in the bilaterally lesioned rats but not in the unilaterally lesioned animals. Unilateral lesions produced increased responsiveness of LC from the lesioned testes as compared to LC from the contralateral testes. Intragonadal modulation of LC function occurs when the function of the seminiferous tubules is impaired.;The possibility that a local factor reached the LC via testicular fluid (TF) was investigated by testing if TF could modify AP by normal LC. TF from controls increased LH stimulated AP by normal LC. TF from spermatogenically disrupted testes resulted in greater net increase of LH stimulated AP by normal LC. This net stimulation of AP by TF cannot be duplicated with LH, FSH, prolactin or GnRH, appears to act post cAMP formation, and is heat-labile.;The stimulatory activity was retained by a Concanavlin A Sepharose column. With gel electrophoresis, at least three glycoprotein bands between 57 and 75 kDa were seen in all samples containing stimulatory activity. Gel filtration fractionation indicated that control TF contained both stimulatory and inhibitory activity. Protein bands between 78 and 118 kDa were present in fractions of control TF containing inhibitory activity, but were absent in TF from lesioned gonads. In unilaterally lesioned animals, the putative inhibitory bands were absent in TF from lesioned testes, but present in TF from spermatogenic testes. The regulation of these proteins appears to be influenced by local conditions associated with spermatogenesis.

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