The overall objective of the research is to determine neuroendocrine mechanisms governing sexual maturation. The domestic sheep will be used as the animal model. The proposed research will extend our working hypothesis on control of the timing of puberty through an increase in frequency of LH pulses. Studies will be conducted to address fundamental issues in regulation of LH secretion by steroid negative feedback, by steroid-independent control, by endogenous opioids and by melatonin. Artificial light treatments will be used extensively to probe the developing neuroendocrine system in order to ascertain the ontogeny of the endogenous melatonin rhythm and its link to the system controlling LH secretion. Measurement of other circadian rhythms by a telemetric system during the early postnatal period will facilitate understanding why the pineal gland of the neonatal lamb does not produce a pattern of melatonin that accords with the prevailing photoperiod. The light requirements for puberty will be studied; lambs, rendered nonphotoperiodic by denervation of the pineal gland, will be exposed to a brief duration (5 weeks) of molatonin treatment to test the hypothesis that one photoperiod has initiated a sequence of events that lead to puberty, puberty can occur in the absence of any prevailing light signals. Moreover, studies will be conducted that bear upon the concepts that an adult seasonal breeder undergoes an """"""""annual puberty"""""""" and that the circannual rhythm of reproduction is innate, rather than established through experience. An investigation will be carried out to determine if the functioning of the system regulating steroid-feedback sensitivity can be separated from that controlling steroid-independent modulation of LH secretion. The involvement of endogenous opioids in the regulation of LH pulse frequency will be examined in the context of photoperiod-induced changes in sensitivity to estradiol feedback inhibition. The research has broad application to the understanding of how puberty is timed in animals, knowledge that will ultimately contribute to greater understanding of normal and delayed puberty in children.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD018394-04
Application #
3315434
Study Section
Reproductive Biology Study Section (REB)
Project Start
1984-03-01
Project End
1991-02-28
Budget Start
1987-03-01
Budget End
1988-02-29
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Malcolm, Karl D; Jackson, Leslie M; Bergeon, Christine et al. (2006) Long-term exposure of female sheep to physiologic concentrations of estradiol: effects on the onset and maintenance of reproductive function, pregnancy, and social development in female offspring. Biol Reprod 75:844-52
Smith, G D; Jackson, L M; Foster, D L (2002) Leptin regulation of reproductive function and fertility. Theriogenology 57:73-86
Nagatani, S; Thompson, R C; Foster, D L (2001) Prevention of glucoprivic stimulation of corticosterone secretion by leptin does not restore high frequency luteinizing hormone pulses in rats. J Neuroendocrinol 13:371-7
Nagatani, S; Zeng, Y; Keisler, D H et al. (2000) Leptin regulates pulsatile luteinizing hormone and growth hormone secretion in the sheep. Endocrinology 141:3965-75
Nagatani, S; Guthikonda, P; Foster, D L (2000) Appearance of a nocturnal peak of leptin secretion in the pubertal rat. Horm Behav 37:345-52
Ohkura, S; Tanaka, T; Nagatani, S et al. (2000) Central, but not peripheral, glucose-sensing mechanisms mediate glucoprivic suppression of pulsatile luteinizing hormone secretion in the sheep. Endocrinology 141:4472-80
Bucholtz, D C; Chiesa, A; Pappano, W N et al. (2000) Regulation of pulsatile luteinizing hormone secretion by insulin in the diabetic male lamb. Biol Reprod 62:1248-55
Foster, D L; Nagatani, S (1999) Physiological perspectives on leptin as a regulator of reproduction: role in timing puberty. Biol Reprod 60:205-15
Kim, S J; Foster, D L; Wood, R I (1999) Prenatal testosterone masculinizes synaptic input to gonadotropin-releasing hormone neurons in sheep. Biol Reprod 61:599-605
Medina, C L; Nagatani, S; Darling, T A et al. (1998) Glucose availability modulates the timing of the luteinizing hormone surge in the ewe. J Neuroendocrinol 10:785-92

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