The milk glands in Mammals constitute one of the most remarkable of secondary sexual characters. Except in their functional relations to the primary organs, the ovaries, and to the uterus, there is nothing sexual about them. They are parts of the skin, being nothing more or less than enormous enlargements of dermal glands, either sebaceous or sudoriparous. Uterine and mammary functions are generally regarded as essentially female characteristics, and are included in the popular idea of the sex of woman. Scientifically, of course, they are not at all necessary or universal features of the female sex, but are peculiar to the mammalian class of Vertebrates in which they have been evolved. Milk glands, then, are somatic sex-characters common to a whole class, instead of being restricted to a family like the antlers in Cervidae. There is not the slightest trace or rudiment of them in other classes of Vertebrates, such as Birds or Reptiles. They are not actually sexual in their nature, since their function is to supply food for the young, not to play a part in the relations of the sexes. What is sexual about them is—firstly, that they are normally fully developed only in the female, rudimentary in the male; secondly, that their periodical development and functional activity depends on the changes which take place in the ovary and uterus. Many investigators have endeavoured to discover the nature of the nexus between the latter organs and the milk glands.
That this nexus is of the nature of a hormone is generally agreed, and may be regarded as having been proved in 1874 when Goltz and Ewald [Footnote: Pflügers Archiv, ix., 1874.] removed the whole of the lumbo-sacral portion of the spinal cord of a bitch and found that the mammae in the animal developed and enlarged in the usual way during pregnancy and secreted milk normally after parturition. Ribbert [Footnote: Fortschritte der Medicin, Bd. 7.] in 1898 transplanted a milk gland of a guinea-pig to the neighbourhood of the ear, and found that its development and function during pregnancy and at parturition were unaffected. The effective stimulus, therefore, is not conveyed through the nervous system, but must be a chemical stimulus passing through the vascular system.
Physiologists, however, are not equally in agreement concerning the source of the hormone which regulates lactation. Starling and Miss Lane-Claypon concluded from their experiments on rabbits that the hormone originated in the foetuses themselves within the pregnant uterus. In virgin rabbits it is difficult to find the milk glands at all. When found the nipple is minute and sections through it show the gland to consist of only a few ducts a few millimetres in length. Five days after impregnation the gland is about 2 cm. in diameter. Nine days after impregnation the glands have grown so much that the whole inner surface of the skin of the abdomen is covered with a thin layer of gland tissue. In six cases by injecting subcutaneously extracts of foetus tissue Starling and Lane-Claypon obtained a certain amount of growth of the milk glands. The hormone in the case of the pregnant rabbit is of course acting continuously for the whole period of pregnancy, while the artificial injection took place only once in twenty-four hours, and the amount of hormone it contained may have been absorbed in a very short time. The amount of growth obtained experimentally in five weeks was less than that occurring in pregnancy in nine days. Extracts of uterus, placenta, or ovary produced no growth, although the ovaries used were taken from rabbits in the middle of pregnancy. In one experiment ovaries from a pregnant rabbit were implanted into the peritoneum of a non-pregnant rabbit, but on post-mortem examination of the latter eleven days later the implanted ovaries were found to be necrosed and no proliferation of milk gland had taken place.
The conclusions of Starling and Lane-Claypon were confirmed by Foa, [Footnote: Archivo d. Fisiologia, v., 1909.] and by Biedl and Königstein, [Footnote: Zeitschrift f. exp. Path. und Therap., 1910.] Foa states that extracts of foetuses of cows produced swelling of the mammae in a virgin rabbit.
O'Donoghue, however, concludes from a study of the Marsupial Dasyurus that the stimulus which upon the milk glands proceeds from the corpora lutea in the ovary. In this animal changes in the pouch occur in pregnancy, which are doubtless also due to hormone stimulation, but which we will not consider here. The most important evidence in O'Donoghue's paper [Footnote: Quart. Journ. Mic. Sci., lvii., 1911-12.] is that development of the milk glands takes place after ovulation not succeeded by pregnancy; that is to say, when corpora lutea are formed but no fertilised ova or foetus are present in the uterus. In one case eighteen days after heat, the milk gland was in a condition resembling that found in the stages twenty-four and thirty-six hours after parturition. In another specimen, twenty-one days after heat, the milk glands were still more advanced, with distended alveoli and enlarged ducts. The alveoli contained a secretion which was almost certainly milk, O'Donoghue states that the entire series of growth changes in these animals up to twenty-one days after heat in identical with that which occurs in normally pregnant animals.
O'Donoghue's conclusion is in agreement with that of Basch,[Footnote: Monatesschr. f. Kinderh. V., No. ix., Dec. 1909.] who states that implantation of the, ovaries from a pregnant bitch under the skin of the back of a one-year-old bitch that was not pregnant was followed by proliferation of the mammary glands of the latter. After six weeks the glands were considerably enlarged, and after eight weeks they were caused to secrete milk by the injection of extract of the placenta. It has to be remembered, however, that the milk glands undergo considerable growth, especially in the human species, at puberty and at every menstruation, or at oestrus in animals, which correspond to menstruation. In these cases there is no question of any influence of the foetus, and experiment has shown that if the ovaries are removed before puberty, the milk glands nor the uterus undergo the normal development and menstruation does not occur. According to Marshall to Jolly [Footnote: Quart. Journ. Exp. Phys., i. and ii., 1906.] the symptoms of oestrus in castrated bitches were found to result from the implantation of ovaries from other individuals in the condition of oestrus.
Before considering further the question of the corpora lutea as organs of internal secretion, we may briefly refer to the origin and structure of these bodies and of other parts of the mammalian ovary. The mature follicle containing the ovum differs from that of other Vertebrates in the fact that it is not completely filled by the ovum and the follicular cells surrounding it, but there is a cell-free space of large size into which the ovum covered by follicular cells projects. In the wall of the follicle two layers are distinguished, the theca externa, which is more fibrous, and the theca interna, which is more cellular. In the connective tissue stroma of the ovary between the follicles are scattered, or in some cases aggregated, epithelioid cells known as the interstitial cells, and it is stated that the cells of the theca interna are exactly similar to the interstitial cells. According to Limon [Footnote: Arch. d'Anat. micr., v., 1902.] and Wallart [Footnote: Arch. f. Gynock, vi. 271.] the interstitial cells are actually derived from those of the theca interna of the follicles. Numbers of ova die without reaching maturity, the follicular cells degenerate, and the follicle becomes filled with the cells of the theca interna, which have a resemblance to those of the true corpus luteum. These degenerate follicles have been termed spurious corpora lutea, or atretic vesicles. The interstitial cells are the remains of these atretic vesicles. The true corpora lutea arise from follicles in which the ova have become mature and from which they have escaped through the surface of the ovary. As a result of the escape of the ovum and the contents of the cell-free space, the follicle contracts and the follicular (so-called granulosa) cells secrete a yellow substance, lutein, and enlarge. Buds from the theca interna invade the follicle and form the connective tissue of the corpus luteum.
Somewhat similar processes take place in the ovaries of Teleostean fishes, as I know from my own observations, but no corpora lutea are formed in these, although the degenerating follicles in course of absorption correspond to corpora lutea. The spawning of Fishes, usually annual, corresponds to ovulation in Mammals, and in the ovary after spawning the numerous collapsed follicles containing the follicular cells may be seen in all stages of absorption. [Footnote: Cunningham, 'Ovaries of Teleosteans.' Quart. Journ. Mic. Sci., vol. xl. pt. 1., 1897.] At other times of the year sections of the ovary show here and there ova which after developing to a certain stage die and undergo absorption with their follicles.
In the higher Mammals (Eutheria) the corpora lutea show a special relation in their development to the occurrence of pregnancy, that is to say, they have a different history when ovulation is followed by pregnancy to that which they have when the ova, from the escape of which they arise, are not fertilised. When fertilisation occurs the corpus luteum increases in size during the first part of the period of gestation (four months, or nearly a half of the whole period in the human species). It then remains without much change till parturition, after which it shrinks and is absorbed. When pregnancy does not occur the corpus luteum is formed, but begins to diminish within ten or twelve days in the human species and is then gradually absorbed. According to O'Donoghue, in the Marsupial Dasyurus there seems to be no difference either in the development of the milk glands or of the corpora lutea between the pregnant and the non-pregnant animal. Sandes [Footnote: Proc. Lin. Soc., New South Wales, 1903.] showed that in the same species the corpora lutea persisted not only during the whole of pregnancy, which Professor J. P. Hill [Footnote: Anat. Anz., xviii., 1900.] estimates at a little over eight days, but during the greater part of the period of lactation, which according to the same authority is about four months. In the specimens of Dasyurus described by O'Donoghue, in which the milk glands developed after ovulation without ensuing pregnancy, normally developed corpora lutea were present in the ovary. Of the five females which he mentions, the first three, one with unfertilised ova in the uteri, two five and six days after heat, could not have been pregnant, but the other two killed eighteen and twenty-one days after heat might, since pregnancy lasts only eight days, have been pregnant, the young having died at parturition or before. To make certain on this point it would have been necessary to examine the ovaries and milk glands of females which had been kept separate from a male the whole time. There is no doubt, however, about the development of the milk glands in the first three specimens, which were certainly not pregnant.
It is difficult to reconcile entirely the evidence described by O'Donoghue from Dasyurus, with that obtained from higher Mammals, although on the whole there is reason to conclude that the corpora lutea have an important influence on the development of the milk glands. According to Lane-Claypon and Starling, if the ovaries and uteri are removed from a pregnant rabbit before the fourteenth day the development of the mammary gland ceases, retrogression takes place, and no milk appears in the gland. If, on the other hand, the operation be performed after the fourteenth day, milk appears within two days after the operation. It is to be concluded from this that the cause of secretion of milk is the withdrawal of a stimulus proceeding from ovary or uterus. But O'Donoghue believes that milk is secreted in Dasyurus when no pregnancy has occurred. Ancel and Bouin [Footnote: C. R. Soc. de Biol., t. lxvii., 1909.] have shown that the growth of the mammary glands was produced in rabbits by the artificial rupture of egg follicles and consequent production of corpora lutea: the growth of the glands continued up to the fourteenth day, after which regression set in. This shows that the development of the milk glands in rabbits is due to the corpora lutea. On the other hand, Lane-Claypon and Starling state that in rabbits the corpora lutea diminish after the first half of pregnancy, while the growth of the milk glands is many times greater during the second half than during the first half of the period, and during the second half the ovaries may be removed entirely without interfering with the course of pregnancy or the normal development of the milk glands. It is evident, therefore, that in rabbits, whatever influence the corpora lutea may have in the first half of pregnancy, they have none in the second half, and that at this period the essential hormone proceeds from the developing foetus or foetal placenta. Again, if it is the withdrawal of a hormone stimulus which changes the milk gland from growth to secretion, it cannot be the corpora lutea which are exclusively concerned even in Dasyurus, for they persist during lactation, while secretion begins shortly after parturition.