Groups of Merino ram lambs were immunized against GnRH either soon after birth (prepubertal)

Groups of Merino ewe lambs were immunized against GnRH either soon after birth (prepubertal) or around puberty (peripubertal) with a prototype commercial preparation and were studied over the following 2 years to determine the long-term effects on reproductive development, function and hormone concentrations. At least 60% of the GnRH-immunized ewes in either treatment group did not experience oestrus and possessed small uteri and small ovaries that lacked follicular development. Growth rates of immunized and control ewes were similar throughout the study. Compared with the increase in plasma LH and FSH concentrations with age in control ewes, the concentrations of these hormones in immunized animals were lower and remained relatively constant from 46 to 90 weeks of age. Plasma FSH concentrations were particularly suppressed in immunized ewes and were significantly (P < 0.05) lower than the control values of 61 and 90 weeks of age. LH release after injection of 1 microgram GnRH at 90 weeks of age was either absent or suppressed in immunized ewes compared with controls. The findings suggest that the lack of GnRH stimulation and consequent deprivation of gonadotrophins, early in the life of ewes, may result in some degree of permanent impairment of hypothalamic and/or pituitary function.

When N-[5-(4-aminophenoxy)pentyl]phthalimide was administered to sheep in sufficient quantities to permit manual removal of the fleece (400 mg/kg body weight orally, or 75 mg/kg body weight intravenously during a period of 48 h), cell division ceased in the wool follicle bulbs within 1 day. Dark-staining bodies (autophagic vacuoles) developed concomitantly in the cytoplasm of the bulb cells. The nuclei of cells in the keratogenous zones of the fibres became pycnotic 2 days after dosing and subsequent keratinization of these portions of the fibres was impaired. All the follicles retrogressed prior to day 7 after dosing, and the root ends which formed on the fibres moved towards the skin surface, reaching the level of the sebaceous glands by day 7. At this time mitotic activity recommenced around the dermal papillae in about 50% of the follicles. A small number of tips of new fibres emerged from the skin surface of some of the depilated sheep by day 14. The root ends on the fibres in the fleeces harvested at days 7-15 were fragmented with various degrees of taper. By 21 days, most follicles were growing emergent fibres. Thickening of the epidermis, increase in sebaceous gland size and decrease in skin thickness occurred in some of the depilated sheep.Smaller doses of the compound (200 mg/kg body weight orally or 40 mg/kg body weight intravenously during 24 h) produced weakness in the wool. Fewer autophagic vacuoles were present in follicle bulbs 1 day after dosing and not all follicles regressed. The weakened region of the fleece contained a mixture of shed fibre ends and continuously growing fibres with thin regions proximal to poorly keratinized lengths of fibre. No change was observed in other components of the skin of the sheep with weakened wool.The follicular changes produced by this compound are similar in some respects to those produced by other depilatory compounds or that occur during natural cyclic hair growth.

Plasma concentrations of growth hormone (GH) are elevated in sheep during undernutrition. The present study attempted to determine whether this increased secretion mediated nutritional effects on reproduction or wool growth, using sheep immunized against growth hormone-releasing hormone and given a low-quality, sub-maintenance diet. Immunization reduced plasma concentrations of GH at all times measured (P < 0·01), through reduced pulse frequency, reduced pulse amplitude, and reduced baseline concentrations. Plasma insulin-like growth factor-1 (1GF-1) was also reduced in the immunized sheep (P < 0·01). Despite this, rates of live-weight loss and wool growth were similar in immunized and control ewes. Plasma concentrations ofLH and FSH were also similar in immunized and control ewes, both during the late luteal phase and after ovariectomy and supplementation with oestradiol and progesterone. Numbers of ovarian follicles and corpora lutea were also unaffected by immunization. It is concluded that high endogenous concentrations of GH in sheep given food below maintenance are necessary to maintain plasma IGF-1, but do not affect the concentration of gonadotropins or ovarian follicular growth. Furthermore, rates of live-weight loss and the depression in wool growth in such animals were also independent of concentrations ofGH or IGF-1.

.-To a suspension of 1,3-dibenzyl-6-aminouracil (3.07 g, 10 mmol) in 20 ml of DMF was added dimethyl acetylenedicarboxylate (1.56 g, 11 mmol) and the mixture was heated at 110°f or 2 hr. To the dark red solution was added 150 ml of ether. The resulting precipitate was filtered and washed with 40 ml of ether to yield 1.62 g (39%), mp 235°. Recrystallization of a 1.1-g sample from DMF-HjO gave 0.9 g: mp 239-240°u v (pH 1) 438 nm (e 5500), 336 (6850), 270 (15,830), (pH 7) 330 (22,400), 273 (7930), (pH 11) 330 (22,100), 273 (7930);