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N Y Lam

Publications and source records attributed to N Y Lam.

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Transplanted gonadotropin-releasing hormone neurons promote pulsatile luteinizing hormone secretion in congenitally hypogonadal (hpg) male mice.

Congenitally hypogonadal (hpg) male mice are unable to synthesize biologically active gonadotropin-releasing hormone (GnRH). Implantation of normal fetal preoptic area tissue containing GnRH neurons into the third ventricle of adult hpg males significantly elevates pituitary levels of luteinizing hormone (LH) and corrects their hypogonadism. In all responding animals, immunoreactive GnRH neurons within the transplant innervate the median eminence of the host. To assess whether gonadal recovery in hpg hosts results from pulsatile secretion of GnRH from grafted neurons, we compared the pattern of variation in plasma LH levels in 19 hpg graft recipients with testicular growth to that of 10 normal adult mice. All animals were castrated prior to receiving an indwelling catheter in the jugular vein. Sequential blood samples were collected (t = 10 min) and assayed for LH. Pulsatile LH secretion was seen in 11 of 19 hpg hosts and in all control mice. While there was great variability between individual animals, measures of baseline LH, LH pulse amplitude and duration, interpulse interval, and LH pulse frequency revealed no difference between hpg graft recipients and normal castrates in their LH pulse pattern. Immunocytochemical analysis of the brain in hpg hosts suggested no correlation between any parameter of pulse activity and individual differences in GnRH cell number or GnRH fiber outgrowth into the median eminence. Sources of variation in LH secretion among graft recipients, and between hpg hosts and normal mice, are discussed. We suggest that transplanted GnRH neurons are capable of integration into a GnRH 'pulse generator' which can support a near-normal pattern of pulsatile LH secretion, leading to testicular growth and steroid production.

Animals

Is the decrease in the hypophysiotropic signal frequency normally observed during the luteal phase important for menstrual cyclicity in the primate?

The two phases of the ovulatory menstrual cycle of the primate are characterized by divergent activities of the GnRH pulse generator. During the luteal phase, LH pulse frequency is significantly reduced below that observed during the follicular phase. In this report we investigate whether the decrease in pulse frequency during the luteal phase is of physiological relevance to normal menstrual cyclicity. We have tested the effect of a pulsatile GnRH infusion given iv at hourly intervals for a period of 8-10 days during the luteal phase on the subsequent three to five cycles in eight female rhesus monkeys. Three of the eight animals received two treatment courses. Amounts of GnRH infused were 1.5 micrograms/pulse (n = 2 trials); 3.0 micrograms/pulse (n = 7); and 4.0 micrograms/pulse (n = 2). LH response to GnRH pulses of 1.5 and 3.0 micrograms resembled spontaneous LH pulses observed during the luteal phase. During the GnRH infusion period, the monkeys were fitted with a primate vest and tethered. Eleven control experiments were performed in these monkeys under similar conditions. GnRH therapy during the luteal phase affected subsequent cycles significantly, while no differences were observed in the control experiments. Overall mean follicular phase length in the control cycle was 13.4 days; it was significantly increased (P less than 0.005) in all post-GnRH treatment cycles to reach 34.4 (+/- 10.9), 43.9 (+/- 12.7), 40.4 (+/- 13.0), and 23.1 (+/- 4.8) days (+/- SE) in the first to fourth post-GnRH cycles, respectively. Progesterone secretion was significantly lower (P less than 0.05) in the first two post-GnRH cycles than in the control cycles: progesterone, 46.4 (+/- 2.1) in all control cycles, decreased to 27.7 (+/- 3.7), 24.8 (+/- 4.3), 34.0 (+/- 5.4), and 32.0 (+/- 6.5) surface units (+/- SE) from the first to fourth post-GnRH cycles, respectively, while luteal phase length remained relatively unchanged. The data indicate that significant disturbances in the menstrual cycle of the rhesus monkey follow imposed changes in the normal frequency pattern of the GnRH hypophysiotropic signal during the luteal phase and suggest that the naturally occurring slowing of GnRH-LH pulse frequency during the luteal phase is a relevant phenomenon in the sequence of events which control menstrual cyclicity.

Animals