Immunization of sheep against GnRH early in life: effects on reproductive function and hormones in ewes.

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.

Immunization of sheep against GnRH early in life: effects on reproductive function and hormones in rams.

Groups of Merino ram lambs were immunized against GnRH either soon after birth (prepubertal) or around puberty (peripubertal) with a prototype commercial preparation and studied over the following 2 years to determine the long-term effects of such immunization on reproductive development, function and hormone concentrations. The treatment was equally effective in suppressing reproductive function and hormones when given at either time. Growth rates of immunized and controls rams were similar throughout the study. Prepubertal immunization delayed testicular growth until the rams were at least 27 weeks of age and some rams had subnormally sized testes even at 115 weeks of age. After peripubertal immunization, the mass of the testes declined and remained regressed until the rams were from 51 to 90 weeks old. There was a significant correlation between total testicular mass at 115 weeks of age and duration (weeks) of suppression of testicular growth (prepubertal, r = -0.7375; peripubertal, r = -0.7132, P < 0.001). Prepubertal immunization markedly delayed separation of the penis from the prepuce. The immunized rams did not display sexual activity until their total testicular mass reached at least 70 g. In control and immunized rams with testicular mass > 100 g, the semen did not differ in the percentage of spermatozoa that were unstained (live), of normal morphology, or showed progressive movement. Compared with the increase in plasma LH and FSH concentrations with age in control rams, the concentrations of these hormones in the immunized animals were lower and remained relatively constant from 46 to 90 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of a seasonal elevation in daytime melatonin levels associated with the rut in fallow bucks (Dama dama): the effect of day length and exogenous melatonin.

The timing of the seasonal reduction in voluntary food intake and hormonal changes associated with the rut were investigated in mature fallow bucks subjected to artificial long-day exposure with and without superimposed melatonin-releasing implants. Circulating testosterone profiles and the period of inappetence, signalling the onset of the period of reproductive activity in untreated bucks under natural photoperiod, were phase-advanced in both treatment groups. In the long-day treated group, these profiles were phase-advanced by 1 week, while in the long-day + melatonin group, the phase advance was 6 weeks compared to the controls. Circulating daytime melatonin, elevated in all three groups, corresponds with seasonal changes in circulating testosterone levels associated with the rut. Prolactin profiles followed ambient photoperiod, being high during natural or artificial long days and low during natural short days. Exogenous melatonin administered during long-day exposure initiated a rapid and reversible decrease in circulating prolactin levels. The elevation in plasma melatonin could not be separated temporally from the seasonal testosterone peak by exposure to long days or to exogenous melatonin. However, this daytime melatonin profile was abolished by the ablation of circulating testosterone following immunization against luteinizing hormone releasing hormone (LHRH). The presence of this endogenous melatonin during daylight was observed only during the rut, as measured in two radioimmunoassays and confirmed by mass spectrometry. It is likely that both testosterone and melatonin influence the onset of the seasonal rut in fallow bucks.

Vaxstrate: an anti-reproductive vaccine for cattle.

This paper describes the development of a vaccine for the prevention of pregnancy in female cattle. The vaccine is based on the established principle that antibodies to the hypothalamic releasing hormone, gonadotrophin releasing hormone (GnRH) block the action of GnRH on pituitary secretion of luteinizing hormone and follicle stimulating hormone, leading to gonadal atrophy in mammals. The vaccine comprises an immunogenic GnRH:ovalbumin conjugate formulated in a novel double adjuvant system and is administered in a two-dose treatment regimen. Field trials have confirmed efficacy and the product, Vaxstrate, has now been registered and commercialized.

Investigation of some amino acid analogues and metabolites as inhibitors of wool and hair growth.

Sheep were given intravenous infusions of ethionine together with cycloleucine or reduced glutathione, in attempts to prevent the inhibition of wool growth by ethionine. Other sheep were given cycloleucine alone to measure effects on wool growth. Twenty-two compounds related to cystine, methionine, ethionine, lysine, phenylalanine and tyrosine were given as intravenous infusions to sheep to investigate their potential as depilatory agents. Nineteen of these compounds were also tested in mice during their first cycle of hair growth. The concurrent administration of cycloleucine with ethionine prevented the weakening of wool fibres caused by ethionine, but reduced glutathione was ineffective. Cycloleucine weakened wool fibres, as judged subjectively, and caused a small reduction in fibre diameter. Selenocystine and selenomethionine caused some hair loss in mice but selenocystine was also toxic. Both seleno-amino acids were toxic for sheep; selenocystine was lethal at 0.025 mmol kg-0.75 and selenomethionine at 0.09 mmol kg-0.75. Doses that permitted survival of sheep did not have depilatory effects. However, the presence of autophagic vacuoles in the cytoplasm of follicle bulb cells of sheep indicated that a toxic dose of selenocystine had potential depilatory activity. Other compounds investigated did not induce loss of wool or hair. Some compounds, notably 3-methylthiopropionic acid and S-(2-aminoethyl)-L-cysteine, were toxic to mice but not sheep. The methionine analogue, methoxinine (O-methyl-DL-homoserine), caused a substantial reduction in the strength of wool fibres and a prolonged alteration of the crimp pattern. It is suggested tentatively that cycloleucine inhibits methionine adenosyltransferase and thereby reduces or prevents the formation of S-adenosylethionine. The failure of various compounds related to methionine and ethionine to have any depilatory activity in sheep supports the view that ethionine influences wool growth via the formation of S-adenosylethionine.

Effects of internally administered N-[5-(4-aminophenoxy)pentyl]phthalimide on wool follicles and skin of sheep.

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.