Experiments are proposed to investigate hypothalamic control of the onset of puberty in the female rhesus monkey. The goal set for this proposal is to test further the hypothesis that an increased release of luteinizing hormone releasing hormone (LHRH) due to maturation of the hypothalamus, is the key factor controlling the onset of puberty, and to determine the mechanisms by which posterior hypothalamic lesions induce precocious puberty. The hypothesis is based upon previous finding that an increase in episodic (diurnal and pulsatile) release of LH occurs during the early phase of puberty and that posterior hypothalamic lesions advance the time of appearance of these hormonal changes as well as the time of menarche and first ovulation. First, the pattern of LHRH release from the median eminence during maturation will be directly determined using a push-pull cannula method. An increase in episodic release of LHRH may occur along with pubertal changes in diurnal and pulsatile LH. Second, a profile of LHRH in precocious puberty induced by posterior hypothalamic lesions will be compared to physiological puberty. Lesions of the posterior hypothalamus may enhance the episodic release of LHRH, resulting in an advancement of puberty. Third, changes in neurotransmitters of the median eminence during the pubertal period will be examined using the push-pull cannula method. Fourth, the nature of hypothalamic inhibition prior to the onset of puberty and the mechanism by which posterior hypothalamic lesions induce precocious puberty will be analyzed. Circulating levels of melatonin, as a possible substance that is involved in suppressed levels of LH before puberty, will be measured during prepubertal through peripubertal periods in both normal and brain-lesioned animals. Moreover, attempts will be made to induce precocious puberty by an hourly application of electrical stimulation to the median eminence, and by infusing substances which may interfere with the inhibitory function of the hypothalamus before puberty. Drugs such as naloxone and quipazine will be examined. Maturational changes in LHRH-containing neurons will also be compared between normal puberty and precocious puberty with posterior hypothalamic lesions. Results from these projects will not only provide evidence to support the proposed hypothesis, but will also clarify the essential role of the hypothalamus in controlling the onset of puberty.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
United States
Zip Code
Kenealy, Brian P; Keen, Kim L; Garcia, James P et al. (2017) Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys. Proc Natl Acad Sci U S A 114:13804-13809
Kenealy, Brian P; Keen, Kim L; Garcia, James P et al. (2015) Prolonged infusion of estradiol benzoate into the stalk median eminence stimulates release of GnRH and kisspeptin in ovariectomized female rhesus macaques. Endocrinology 156:1804-14
Kurian, Joseph R; Keen, Kim L; Kenealy, Brian P et al. (2015) Acute Influences of Bisphenol A Exposure on Hypothalamic Release of Gonadotropin-Releasing Hormone and Kisspeptin in Female Rhesus Monkeys. Endocrinology 156:2563-70
Joers, Valerie; Dilley, Kristine; Rahman, Shahrose et al. (2014) Cardiac sympathetic denervation in 6-OHDA-treated nonhuman primates. PLoS One 9:e104850
Al├žin, E; Sahu, A; Ramaswamy, S et al. (2013) Ovarian regulation of kisspeptin neurones in the arcuate nucleus of the rhesus monkey (macaca mulatta). J Neuroendocrinol 25:488-96
Kenealy, Brian P; Kapoor, Amita; Guerriero, Kathryn A et al. (2013) Neuroestradiol in the hypothalamus contributes to the regulation of gonadotropin releasing hormone release. J Neurosci 33:19051-9
Kurian, Joseph R; Terasawa, Ei (2013) Epigenetic control of gonadotropin releasing hormone neurons. Front Endocrinol (Lausanne) 4:61
Terasawa, Ei; Guerriero, Kathryn A; Plant, Tony M (2013) Kisspeptin and puberty in mammals. Adv Exp Med Biol 784:253-73
Guerriero, Kathryn A; Keen, Kim L; Terasawa, Ei (2012) Developmental increase in kisspeptin-54 release in vivo is independent of the pubertal increase in estradiol in female rhesus monkeys (Macaca mulatta). Endocrinology 153:1887-97
Terasawa, Ei; Kenealy, Brian P (2012) Neuroestrogen, rapid action of estradiol, and GnRH neurons. Front Neuroendocrinol 33:364-75

Showing the most recent 10 out of 69 publications