Summary. Goats were hemimastectomized during Weeks 5 or 8 of lactation. The milk yield of the remaining gland (the test gland) usually increased in a compensatory fashion after the operation, although the degree of response varied from no response to a 50% increase. The glands of those goats that responded and received no further treatment maintained an increased milk yield for the duration of the lactation. Changes in the size and composition of the gland were investigated by a combination of udder volume and biopsy in some goats. Increases in both gross size and total DNA content (DNAt, a measure of cell number) were observed in all of these, although the timing of the response varied between individuals. Overall, cell population size was maintained for at least 18 weeks after hemimastectomy whereas in control (unoperated) goats DNAt decreased by 35% over a similar period.
C. H. Knight and M. Peaker
The first obvious statement is that the mammary gland is an intriguing structure, and that its development is one of the most fascinating aspects. During the lifetime of the animal the mammary gland probably undergoes more and greater changes in size, structure, composition and activity than any other tissue or organ. These changes start during fetal life and continue even after the gland has reached maturity since it waxes and wanes during successive reproductive cycles. In its most advanced state, that of full lactation, the gland possesses vast numbers of specialized secretory cells (parenchyma) together with supporting connective and adipose tissue (stroma); it may produce considerably more than its own weight of secretion every day or, in energetic terms, as many joules per day as it contains in its own mass.
The second obvious statement is that the actual yield of milk is a function of the amount produced
C. J. Wilde, A. J. Henderson, and C. H. Knight
Summary. Metabolic adaptations of goat mammary tissue during pregnancy and lactation were monitored in serial biopsies of the tissue. Changes in the synthetic capacity of secretory cells were studied by combining measurements of enzyme activities with short-term culture of mammary explants to measure lactose, casein and total protein synthesis. By these criteria, the main phase of mammary differentiation began in late pregnancy and was essentially complete by Week 5 of lactation, coinciding with the achievement of peak milk yield. While milk yield declined after Week 5, the activities of key enzymes expressed per mg DNA and the rates of lactose and casein synthesis in mammary explants were maintained over a considerable period. The results suggest that changes in the synthetic capacity of epithelial cells may account for much of the rise in milk yield in early lactation, but are not responsible for the declining phase of milk production characteristic of lactation in ruminants.
C. H. Knight, C. J. Wilde, B. J. McLeod, and W. Haresign
Summary. A specific sheep LH radioimmunoassay was validated for the measurement of goat LH, and used to monitor luteal-phase LH episodes and the preovulatory LH surge in progestagen sponge-synchronized cycling goats. No luteal-phase LH episodes were detected during 12 h of frequent (15-min) blood sampling in 2 goats. A preovulatory LH surge was recorded in 5/5 goats, with a mean amplitude of 45·4 ± 7·2 ng/ml and a mean time of onset of 38·4 ± 1 ·2 h after removal of a progestagen-impregnated sponge. In anoestrous goats, single i.v. injections of 1000 and 2000 ng GnRH induced LH episodes with a mean amplitude of 2·04 ± 0·11 and 3·67 ± 0·06 ng/ml respectively, but injections of 250 or 500 ng did not consistently elevate LH concentrations. Progestagenprimed, seasonally anoestrous lactating goats were treated with repeated injections of 1500 ng GnRH (every 2 h for 52 or 78 h) in May 1985 or 1986. All 10 had kidded in March of the same year, and were consequently at peak lactation at the time of GnRH treatment. A preovulatory LH surge was detected in 9 goats with a mean time of onset of 59·5 ± 2·9 h (1985) or 39·6 ± 3·3 h (1986) after vaginal sponge removal. All animals displayed oestrus and ovulated, and 9 of the goats were mated: in 5 of these animals pregnancies were successfully carried to term.
The results show episodic LH release in response to GnRH and indicate that ovulation can be induced in seasonally anoestrous goats, even at peak lactation, and normal pregnancies may result.
Keywords: goats; LH; GnRH; induced oestrus
P. A. Fowler, C. H. Knight, G. G. Cameron, and M. A. Foster
Summary. A technique is described for the in-vivo determination of mammary gland size and gross composition in goats by using nuclear magnetic resonance imaging (MRI). The volume of test objects determined with MRI had an error of +0·4 ± 1·6% of the actual volume. In lactating goats the in-vivo MRI estimate of mammary parenchymal volume was significantly greater than, but highly significantly correlated with, the weight of parenchyma determined post mortem (for the whole udder, r = 0·88, P < 0·001; for individual glands, r = 0·85, P < 0·001), MRI-determined estimates of the volume of fluid within the mammary gland were within 1·2% of the volume of milk removed from the udders after imaging. The spin-lattice (T1) relaxation time of the whole udder correlated closely with the volume of fluid within the udder. The T1 relaxation time of parenchymal tissue measured in vivo did not differ significantly from that determined immediately after post-mortem excision.
Keywords: mammary gland; magnetic resonance imaging; methodology; goat; lactation
P. A. Fowler, C. H. Knight, G. G. Cameron, and M. A. Foster
Summary. Mammary development and regression were measured in goats in vivo using magnetic resonance imaging (MRI). Measurements were made during the first and second cycles of pregnancy, lactation and involution.
In primiparous goats, an exponential pattern of growth was evident during gestation and for the first 2 weeks of lactation. Parenchyma volume correlated significantly with milk yield across goats during early lactation, and across stage of lactation within goats. Milking was discontinued in Week 26 of the first lactation. Involution was characterized by an initial accumulation of fluid (over 2 days) followed by reabsorption; parenchyma volume did not decrease significantly until the 3rd week of involution, which was also the time at which these goats were mated to start their second gestation. Their udders still contained significant quantities of fluid (40–60% of the gross volume), but parenchyma volume was also greater (by 4·7-fold) than in goats beginning their first gestation. By Week 15 of gestation there was no longer a parity difference in parenchyma; the udders of first-gestation goats had grown significantly, but those of second-gestation goats had not. Conversely, between gestation Week 15 and laction Week 2 mammary growth was significantly more rapid in the second cycle, such that the udder was larger at the start of the second lactation.
Keywords: mammogenesis; mammary gland; lactation; pregnancies; goats; MRI
N. Jenkins, P. G. Knight, C. M. Howles, B. A. Morris, and G. M. H. Waites
Summary. Passive immunization of male lambs against oestradiol-17β from 2 to 16 weeks of age significantly elevated androgen concentrations in plasma and depressed the median eminence content of dopamine. Removal of endogenous oestrogens had no significant effects on plasma FSH, LH or prolactin concentrations or on testicular growth and hypothalamic content of GnRH. These results suggest that endogenous oestrogens may indirectly suppress testicular androgen secretion by exerting a stimulatory influence on hypothalamic dopaminergic neurones, which in turn may inhibit GnRH secretion by the median eminence.
D. S. Tannetta, M. D. Fray, J. H. M. Wrathall, E. C. L. Bleach, R. G. Glencross, and P. G. Knight
The aim of this study was to determine whether supplementary treatment with recombinant bovine growth hormone(rbGH) can enhance the ovulatory response of ewes to inhibin immunization. Crossbred ewes (n = 20) were actively immunized against bovine inhibin a1–29 peptide conjugate while 20 ewes served as controls. Oestrus was synchronized using progestagen sponges and ewes were allocated to four groups: control ewes (n = 10); control ewes given rbGH (n = 10); inhibin-immunized ewes (n = 10) and inhibin-immunized ewes given rbGH (n = 10). A single s.c. dose of rbGH (50 mg) was given 7 days before sponge removal. Blood was collected for measurement of inhibin antibody titre, and concentrations of insulin-like growth factor I (IGF-I), FSH, oestradiol and progesterone. Ovulation, pregnancy and lambing rates were also recorded. All inhibin-immunized ewes produced antibodies that bound125I-labelled (32 kDa) inhibin. The concentration of FSH in the plasma of the ewes after the second booster inhibin immunization was higher than that in control ewes (P < 0.005). Treatment with rbGH promoted a 2–3-fold increase in plasma concentration of IGF-I (P < 0.001); the response was less (P < 0.01) in immunized compared with control ewes. Treatment with rbGH alone had no significant effect on the concentration of FSH or oestradiol or on ovulation rate or litter size. Overall, inhibin-immunized ewes had higher mean FSH concentrations (P < 0.002), higher preovulatory oestradiol surges (P <0.05) and higher progesterone concentrations in the luteal phase (P < 0.0001). Treatment with rbGH reduced the effects of immunization on FSH (P < 0.01) and progesterone (P < 0.02) concentrations. Immunized ewes showed a threefold increase in ovulation rate (P < 0.001) and a 1.8-fold increase in litter size (P <0.05) compared with control ewes. In immunized ewes given rbGH, ovulation rate was increased by a factor of 2.2 and litter size by a factor of 1.8. In conclusion, these data do not support the hypothesis that supplementary treatment of ewes with rbGH to raise plasma IGF-I concentrations (and presumably intraovarian IGF-I) can enhance the ovulatory response to inhibin immunization.
Rachel C Hirst, Margaret H Abel, Vivienne Wilkins, Christine Simpson, Phil G Knight, Fu-Ping Zhang, Ilpo Huhtaniemi, T Rajendra Kumar, and Harry M Charlton
Measurement of inhibins A and B in the serum of normal cyclic rodents has implicated FSH in the regulation of these peptides within the ovary. To extend these observations we have used a panel of mutant mice carrying mutations which affect either the production of, or the ability to respond to, FSH and LH. As a consequence, the females are infertile and show different degrees of follicular development. The aim of this study was to measure inhibin gene transcription in the ovaries of these mutant females together with inhibin protein levels in ovaries and serum and to relate these to follicular development within the ovary. Comparison was made with a pool of normal/heterozygous females. In hpg females where lack of GnRH production results in the absence of gonadotropin synthesis, in FSHβ knockout (FSHβKO) females where disruption of the gene encoding FSHβ results in the absence of FSH production, and in FSH receptor knockout (FSHRKO) females which are unable to respond to circulating FSH, follicular development remains at the pre-antral stage in these three mutants. Only in the hpg females were common inhibin α subunit mRNA levels significantly lower than normal. In these three mutants, however, mRNA levels for both the βA and βB subunits were extremely low compared with normal mice. At the protein level, neither inhibin A nor B was detected in the serum of these three mutants; however inhibin B, albeit at very low levels, was detectable within the ovaries. These observations confirm a major role for FSH in the control of transcription of the βA and βB genes but suggest that the constitutive transcription of the alpha subunit is less dependent on FSH. In contrast, in LH receptor knockout (LuRKO) female mice inhibin βA subunit mRNA levels were similar to those measured in normal/heterozygous females but levels of inhibin α and βB subunit mRNAs were significantly higher than in the normal group. This was reflected in significantly higher inhibin B protein levels in ovaries and serum. An inability to respond to LH combined with high circulating levels of FSH leads to a high proportion of antral follicles in LuRKO females, with granulosa cells constituting the major cell type within the ovary. The high percentage of antral granulosa cells is likely to account for the significantly higher levels of inhibin B production in these ovaries.