A sustained volley of high-frequency pulses of GnRH secretion is a fundamental step in the sequence of neuroendocrine events leading to ovulation during the breeding season of sheep. In the present study, the pattern of GnRH secretion into pituitary portal blood was examined in ewes during both the breeding and anestrous seasons, with a focus on determining whether the absence of ovulation during the nonbreeding season is associated with the lack of a sustained increase in pulsatile GnRH release. During the breeding season, separate groups (n = 5) of ovary-intact ewes were sampled during the midluteal phase of the estrous cycle and following the withdrawal of progesterone (removal of progesterone implants) to synchronize onset of the follicular phase. During the nonbreeding season, another two groups (n = 5) were sampled either in the absence of hormonal treatments or following withdrawal of progesterone. Pituitary portal and jugular blood for measurement of GnRH and LH, respectively, were sampled every 10 min for 6 h during the breeding season or for 12 h in anestrus. During the breeding season, mean frequency of episodic GnRH release was 1.4 pulses/6 h in luteal-phase ewes; frequency increased to 7.8 pulses/6 h during the follicular phase (following progesterone withdrawal). In marked contrast, GnRH pulse frequency was low (mean less than 1 pulse/6 h) in both groups of anestrous ewes (untreated and following progesterone withdrawal), but GnRH pulse amplitude exceeded that in both luteal and follicular phases of the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous studies demonstrated that the thyroid gland is required for the changes in LH secretion that lead to the end of the breeding season of female sheep, a reproductive transition generated within the ewe by an endogenous annual rhythm. The present study tested the hypothesis that this role of the thyroid is mediated via the GnRH neurosecretory system. The pulsatile secretion of GnRH into hypophyseal portal blood and LH into peripheral blood, as well as the neuroanatomical distribution of GnRH neurons and their light microscopic morphology, were compared among anestrous ewes and thyroidectomized (THX) ewes that failed to make the transition to the anestrous season. The study was conducted under photoperiodic conditions in which the transition to anestrus was generated by the endogenous rhythm. Each animal was ovariectomized and treated sc with a constant release implant of estradiol to normalize gonadal steroid status among thyroid-intact and THX ewes. High frequency pulses of GnRH and LH were evident in THX ewes that failed to make the transition to anestrus, whereas pulsatile secretion of GnRH and LH was generally not observed in thyroid-intact controls that had entered anestrus. This marked effect of thyroidectomy on GnRH secretion was not associated with widespread changes in the total number, distribution, or light microscopic morphology of GnRH neurons in the hypothalamus and preoptic area. Our finding that pulsatile secretion of GnRH is elevated in THX ewes that fail to make the transition to anestrus supports the hypothesis that the thyroid gland is required for the endogenously generated switch in function of the GnRH neurosecretory system that leads to the end of the breeding season of the ewe.

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are neurodegenerative lysosomal storage diseases predominantly affecting children. Single administration of brain-directed lentiviral or recombinant single-stranded adeno-associated virus 9 (ssAAV9) vectors expressing ovine CLN5 into six pre-clinically affected sheep with a naturally occurring CLN5 NCL resulted in long-term disease attenuation. Treatment efficacy was demonstrated by non-invasive longitudinal in vivo monitoring developed to align with assessments used in human medicine. The treated sheep retained neurological and cognitive function, and one ssAAV9-treated animal has been retained and is now 57 months old, almost triple the lifespan of untreated CLN5-affected sheep. The onset of visual deficits was much delayed. Computed tomography and MRI showed that brain structures and volumes remained stable. Because gene therapy in humans is more likely to begin after clinical diagnosis, self-complementary AAV9-CLN5 was injected into the brain ventricles of four 7-month-old affected sheep already showing early clinical signs in a second trial. This also halted disease progression beyond their natural lifespan. These findings demonstrate the efficacy of CLN5 gene therapy, using three different vector platforms, in a large animal model and, thus, the prognosis for human translation.

Although it is known that skeletal bone depletion occurs during antler growth in deer, it is not clear whether repletion of the skeleton takes place before or after completion of antler development. This study attempted to correlate repeated scanning electron microscopic measures of ilium and rib bone porosity from six approximately 2‐monthly biopsy samples (using back‐scattered imaging) and biochemical markers of bone turnover (serum hydroxyproline and osteocalcin concentrations) taken for 11 months with antler growth in six red deer stags. No changes were detected in ilium samples but changes in porosity of rib bones and an elevation of the biochemical markers indicated that skeletal depletion occurred during the antler growth period. However, the decrease in rib bone porosity and decline in markers of bone turnover took place before completion of antler growth, indicating that a considerable amount of skeletal repletion could have occurred whilst antlers were also undergoing bone accretion. This latter finding extends the current view of antler growth being accompanied by a form of reversible osteoporosis in the skeleton by showing that there is a period when the antlers and skeleton are both undergoing net bone formation. Anat Rec 256:14–19, 1999.

Summary.: Prepubertal red deer hinds were subjected to shortened daily photoperiod (8 h light per day, N = 3) or a daily (afternoon) melatonin injection (N = 4) for 83 days starting on 8 January, 2 weeks after the summer solstice. Compared with control hinds (N = 3) these treatments caused premature moulting of summer pelage, reduced serum prolactin concentrations to barely detectable levels about 34 days earlier than usual and advanced the date of mating. Calves were born earlier (P < 0·005) in the hinds exposed to a shortened photoperiod (12 November ± 1·7 days) and melatonin treatment (11 November ± 3·2 days) than in control hinds (13 December ± 7·9 days). Serum progesterone levels recorded before the first detected oestrus indicated that silent ovulations had occurred in many of the hinds (6 of 10) in this experiment. This study demonstrated the role of shortened daily photoperiod in red deer and indicated that the effects of reduced photoperiod observed were mediated by melatonin.