MAMMARY GLAND AND LACTATION 



607 



tions it is convenient to refer to the ingeni- 

 ous tlieory put forward by Meites and 

 Turner (1942a, b; 1948) which was based on 

 their extensive investigation of the pro- 

 lactin content of the pituitary in various 

 physiologic and experimental states. Ac- 

 cording to Meites and Turner, estrogen 

 elicits the secretion of prolactin from the 

 anterior pituitary thereby causing lacto- 

 genesis, whereas progesterone is an inhibi- 

 tory agent, operative in pregnancy, inhibit- 

 ing or over-riding the lactogenic action of 

 estrogen. The induction of lactation was 

 thus ascribed to a fall in the body level 

 of progesterone relative to that of estrogen 

 heheved to occur at the time of parturition. 

 Subsequent studies in the rabbit by jVIeites 

 and Sgouris (1953, 1954) revealed that 

 combinations of estrogen and progesterone 

 could inhibit, at the mammary gland level, 

 the lactogenic effects of exogenous prolactin. 

 This effect was, however, relative and by in- 

 creasing the prolactin or decreasing the ster- 

 oids, lactogenesis ensued. Inasmuch as the 

 theory of Meites and Turner did not take 

 into account the eventuality that estrogen 

 and progesterone act at the level of the mam- 

 mary gland, Meites ( 1954) modified the con- 

 ('ei)t, postulating that milk secretion was 

 held in check during pregnancy first by the 

 combined effect of estrogen and proges- 

 terone which make the mammary gland re- 

 fractory to prolactin and, secondly, by a 

 low rate of prolactin secretion. The role of 

 progesterone in over-riding the stimulatory 

 effect of estrogen on the pituitary he now 

 considered to be of only minor importance. 

 Meites also explained the continuance of 

 lactation in pregnant animals by postulat- 

 ing that the initial level of prolactin was 

 sufficiently high as a result of the suckling 

 stimulus to overcome the inhibitory action 

 of the ovarian hormones on the mammary 

 gland. One of us (Folley, 1954, 1956) put 

 forward a tentative theory, combining vari- 

 ous features of previous hypotheses, which 

 seemed capable of harmonizing most of 

 the known facts regarding the initiation of 

 milk secretion. In this it was emphasized 

 that measurements of the prolactin content 

 of the pituitary were not necessarily indica- 

 tive of the rate of prolactin release (a recent 

 study bv Grosvenor and Turner (1958c) 



lends further support to this contention) 

 and were best considered as largely ir- 

 relevant; low circulating levels of estrogen 

 activate the lactogenic function of the an- 

 terior pituitary whereas higher levels tend 

 to inhibit lactation even in the absence of 

 the ovary; lactogenic doses of estrogen 

 may be deprived of their lactogenic action 

 by suitable doses of progesterone, the com- 

 bination then acting as a potent inhibitor 

 of lactation, this being the influence oper- 

 ating in pregnancy; at parturition the rela- 

 tive fall in the progesterone to estrogen ratio 

 removes the inhibition which is replaced by 

 the positive lactogenic effect of estrogen 

 acting unopposed. 



It was observed by Gaines in 1915 that 

 although a colostral secretion accumulated 

 in the mammary gland during pregnancy, 

 the initiation of copious secretion was as- 

 sociated with functioning of the contractile 

 mechanisms in the udder responsible for 

 milk ejection; later Petersen (1944) also 

 suggested that the suckling or milking stim- 

 ulus might be partly responsible for the 

 onset of lactation. Recent studies have pro- 

 vided evidence that this may well be so, 

 and these will be considered later when dis- 

 cussing the role of the suckling and milking 

 stimulus in the maintenance of milk secre- 

 tion (see page 611). 



During the past decade a fair amount of 

 information has been obtained about the 

 biochemical changes which occur in mam- 

 mary tissue near the time of parturition, 

 and which are almost certainly related to 

 lactogenesis. The earlier work has been re- 

 viewed in some detail by one of us (Folley, 

 1956) and need only be referred to briefly 

 here. 



Folley and French (1949), studying rat 

 mammary gland slices incubated in media 

 containing glucose, showed that — QOo in- 

 creased from a value of about 1.3 in late 

 pregnancy to a value of about 4.4 at day 

 1 of lactation, and thereafter increased 

 still further. At the same time the R.Q. 

 which was below unity (approximately 

 0.83) at the end of pregnancy, increased to 

 unity soon after parturition, and by day 

 8 had reached a value of 1.62 at approxi- 

 mately which level it remained for the rest 

 of the lactation period. In accord with the 



