THE CYCLIC CHANGES IN THE MAMMARY GLAND UNDER NORMAL AND PATHOLOGICAL CONDITIONS : I. THE CHANGES IN THE NON-PREGNANT GUINEA PIG.

1. A definite cycle exists in the mammary gland of the non-pregnant guinea pig which corresponds to the cycle in the ovary and uterus. This cycle can be presented through a curve in which the ordinates represent the degree of activity of the gland in a series of animals, and the abscissae the time since ovulation (period of sexual cycle). The curve passes through a first maximum at the time of heat and ovulation and gradually falls. The minimum is reached on the 6th day and continues until the 15th day after ovulation. Next begins the period when a new ovulation is imminent and the number of the proliferating glands again increases. We see. then that during the normal cycle the presence of well preserved, functioning corpora lutea does not lead to proliferation, neither do mature follicles have such an effect. On the other hand, the absence or degeneration of the corpora lutea is required to insure the proliferation of the mammary gland in the first period of the sexual cycle. If the sexual period is experimentally prolonged, we find in some instances proliferation, while in others it is absent. As far as we can determine at the present time, two factors seem to favor proliferation of the mammary gland under these conditions: (1) the presence of well preserved corpora lutea, particularly if they are associated with well preserved experimentally produced deciduornata, and (2) the imminence of a new period of heat. The connection between good corpora lutea and good deciduornata and the presence of proliferating mammary glands at this stage of the sexual cycle is, however, not absolute. There are cases in which a proliferating gland is associated with some degeneration of the corpus luteum. Or on the other hand a well preserved corpus luteum is associated with a non-proliferating gland. In some of the latter cases the simultaneous presence of a necrotic deciduorna may perhaps explain the lack of proliferation in the mammary gland. However, in the majority of cases we found the presence of good corpora lutea and good deciduomata associated with a proliferating mammary gland. Whether a living corpus luteum as such is able to produce proliferation of the gland is as yet doubtful. 2. Extirpation of the ovaries prevents not only the proliferation of the mammary gland associated with the first stage of the sexual cycle, the condition of heat and ovulation no longer taking place in castrated animals, but in all probability also inhibits the proliferation of the mammary gland which occurs under certain conditions towards the end of the sexual cycle, or in instances of experimentally prolonged sexual cycle in which well preserved corpora lutea and deciduornata are present. 3. In animals in which the ovaries were hypotypical, the mammary glands were in an inactive condition. The presence of hypotypical ovaries has the same influence on the mammary gland as castration. In the majority, but not in all of these cases well preserved corpora lutea were absent. 4. Complete extirpation of the corpora lutea seems directly or indirectly to prevent the secondary proliferation of the mammary gland, which occurs during the latter part of the sexual cycle or during an experimentally prolonged cycle, in cases in which the extirpation is not followed at once by a new ovulation. This conclusion we consider, however, merely as suggested, not yet as definitely established through our results. On the other hand, the primary proliferation of the mammary gland, during the first stage of the sexual cycle, as well as ovulation and the objective signs of heat, is accelerated through complete extirpation of the corpora lutea. Thus the effect of extirpation of the corpora lutea differs from the effect of castration, in that after the latter neither a new heat nor the primary proliferation of the mammary gland occurs. As one of the authors has pointed out previously, the absence of functioning corpora lutea and the presence of either well developed ovarian follicles or of mature follicles are necessary for the occurrence of heat and ovulation. The same conditions are prerequisites for the primary proliferation of the mammary gland. 5. In cases in which the whole or almost the whole uterus had been extirpated, the corpora lutea were well preserved and the mammary gland was proliferating.