Hormonal Control of Lactation
The problems involved in the hormonal control of lactation are extremely complex, and researches now in progress, while adding to our knowledge of the factors at work, have not led to the postulation of any all-embracing or coherent theory. Ample evidence for this statement is given in the comprehensive review by Folley,' to whose work we referred in a leading article on lactation in July of last year. At the moment the chief interest in this country is focused on the actions of oestrogens and pituitary fractions and their relations. It is by now well established that mammary development may be incited in most mammals by combined treatment with an oestrogen and progesterone. In general, oestrogens appear to stimulate duct development and progesterone appears to be responsible for alveolar growth. There is no clear-cut evidence that these actions are direct, for experiments in hypophysectomized animals. have given conflicting results in the hands of different workers. In this connexion Speert2 performed an interesting experiment by painting the left nipples of immature male monkeys with an alcoholic solution of oestrone, the right nipples being painted with alcohol alone. He found that the oestronetreated mammae enlarged while the control right nipples were uiaffected, which goes to show that the pituitary was not involved. This conclusion, however, at present applies only to the mammary glands of the immature male monkey, because one of the most confusing factors in research on lactation has been the quite different results obtained by similar procedures in different species and in the different sexes of the same species. The technique of unilateral inunction does, however, provide a method for testing the direct action of hormones absorbed through the skin without removing the animal's own glands, which inevitably results in undesirable and usually uncontrollable secondary effects. Turning to the question of the secretion of milk by the mammary glands when they are fully developed, the pituitary is found to be accepted as the most important factor at work. It is perhaps unfortunate that the early researches of Riddle showed that anterior pituitary extracts which initiate lactation in a variety of species would also cause the growth of crop-glands in the pigeon. This was made the basis of an assay method for preparations and was almost universally adopted. It is only lately that it has been appreciated that this method of assay has distinct disadvantages. It is now realized that an extract capable of stimulating the pigeon's crop-gland does not necessarily initiate milk secretion in mammals. The commercial preparations of prolactin at present available are usually standardized by the crop-gland response, a fact which may accouint for conflicting clinical reports. Folley' therefore proposes that the name " prolactin " should be confined to crop-stimulating activity, and Folley and Young3 suggest the term " galactopoietic factor " for the anterior pituitary fraction responsible for increasing the milk yield of an animal already producing milk. " Lactogenic " is applied to the initiation of lactation in hypophysectomized animals. Folley and Young in their experiments showed that injections of crude anterior pituitary extracts increase the milk yield in cows in declining lactation to a greater extent than do purer preparations containing seven times as much prolactin (crop-stimulating) activity. This leaves open the question whether prolactin is galactopoietic, but proves that there is a distinct galactopoietic factor in the pituitary apart from a prolactin, or a principle which, acting with prolactin, has a synergistic galactopoietic effect. The present difficulty
On the Protein Nature of Prolactin and of Follicle-Stimulating Hormones
Summary Prolactin is a protein-like substance which at pH 8.0 is almost completely destroyed by trypsin in 2 hours at 37°C. In confirmation of previous work though using the bird testis instead of the rodent ovary to test potency, it is found that the follicle-stimulating hormone obtained from the anterior pituitaries of cattle is very rapidly destroyed by trypsin under the above-named conditions. The methods used in the separation and purification of prolactin suggest that this hormone is a protein, but since it has not yet been obtained in a pure state the possibility of its adsorption on inert protein is not thus excluded. It is therefore desirable to learn whether prolactin is affected by tryptic digestion. That prolactin is rapidly destroyed by trypsin is shown by the data of Table I. Almost complete destruction in 2 hours by a purified trypsin is obtained. The prolactin preparation used in this test was relatively pure and highly potent. Both the control and digest were, at the beginning of the test, at pH 8.0 and were similarly kept at 37°C. At pH 8.0 we have repeatedly found that prolactin will withstand boiling for 1 hour with only slight or moderate loss of potency. No earlier observations on the effect of digestive enzymes on prolactin have been reported. The rapid destruction of follicle-stimulating hormone (F.S.H.), obtained from the anterior pituitaries of beef by methods previously described, 1 is shown by the data of Table II. The testes of both birds given F.S.H., heated at pH 8.0 but not subjected to trypsin, are indicated as having increased by something more than 500%. The testes of all of the 4 birds receiving the trypsin digest (birds I and J got double dosage) showed only or relatively insignificant gains in weight. Since size increase in testes of the immature dove represents a specific response to the F.S.H. (here the weight is not increased by a Prolan B factor) this result has definite significance. Under these conditions still other relatively pure preparations of F.S.H. have been shown to withstand heating to 37° for 2 and for 4 hours with little loss of potency. A quite different test for F.S.H. potency has been used in another study; that test likewise shows that trypsin rapidly destroys the F.S.H. derived from both pituitary and pregnant urine.
Serum Profiles of Luteinizing Hormone, Oestradiol and Cholesterol and Ovarian Functions in Layer Poultry Birds (Gallus domesticus) Fed Diets Containing Furazolidone
This study was carried out to assess the serum profiles of luteinizing hormone (LH), oestradiol, cholesterol and ovarian functions in layer poultry birds (Rhode Island Red;Gallus domesticus) fed a diet containing various concentrations of furazolidone (FZ). A total of 40 birds were randomly assigned to receive FZ 0, 200, 400 or 800 mg/kg feed (ppm) daily during the pre-laying age, i.e. 13–18 weeks (for 5 weeks). Blood samples were collected at weekly intervals. Concentrations of LH and oestradiol in serum were estimated at alternate weeks using radioimmunoassays. Serum cholesterol levels were analysed by an enzymatic calorimetric method. Furazolidone administration was terminated at the 18th week of age. The birds were sacrificed at 22nd week of age and ovarian tissues were processed for morphometric studies. Serum LH, oestradiol and cholesterol levels were affected by age (p<0.001) and FZ dose (p<0.001). Serum LH and oestradiol levels were lower (p<0.05) in birds receiving FZ 800 mg/kg feed daily compared with the controls, whereas serum cholesterol profiles were lower (p<0.05) in all FZ-administered groups than in the control group. The mean weight of ovaries having no yolky follicles observed in the group receiving FZ 400 or 800 mg/kg feed per day was reduced (p<0.05) compared with the control group. Dosing FZ at 800 mg/kg feed per day reduced (p<0.05) the mean volume of ovaries having no yolky follicles compared with the control group. In birds receiving FZ 800 mg/kg feed per day, the mean length of the oviduct was reduced (p<0.05) as compared with the control group. Morphometric studies revealed that the mean number of oocytes with diameter in the range 401–800 μm decreased (p<0.05) in birds fed FZ 400 or 800 mg/kg feed per day. Initial egg production was affected by age (p<0.001) and dose (p<0.001) of FZ. The mean number of eggs laid by different groups revealed that egg production was reduced (p<0.05) in birds receiving FZ 800 mg/kg feed per day as compared with the controls. The present data suggest that FZ causes suppression in serum profiles of LH, oestradiol, cholesterol and ovarian functions in Rhode Island Red layer poultry birds. Therefore, great care must be taken with use of FZ in layer poultry birds (Gallus domesticus) with regard to dosage and duration of administration.