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MAXINE GRIFFITHS, K. J. COOPER, and D. B. CRIGHTON

It is established that stimuli associated with the presence of a sexually mature male can influence the oestrous cycle of the underfed rat (Cooper & Haynes, 1967). This effect is still present when physical contact between the sexes is prevented, the lengthened and irregular cycles characteristic of undernutrition becoming significantly shorter (McNeilly, Cooper & Crighton, 1970; Purvis, Cooper & Haynes, 1971). A similar response to the proximity of the male has been demonstrated in the mouse, the lengthened and irregular oestrous cycles usually observed when mice are grouped not being found in the presence of a male (Whitten, 1957). Castration of the male prevented the acceleration of oestrous behaviour, but the stimulus value of the male for the female returned following androgen therapy (Bronson & Whitten, 1968). The object of the work

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A. B. M. ANDERSON, C. G. PIERREPOINT, T. JONES, K. GRIFFITHS, and A. C. TURNBULL

Summary.

The metabolism, in vitro, of isotopically-labelled pregnenolone and progesterone by foetal and adult sheep adrenals has been investigated. Both substrates were almost completely metabolized by the adult tissue, whereas, in the case of the foetus, only pregnenolone showed extensive metabolism. The adult adrenal converted pregnenolone mainly to cortisol, corticosterone and 11-deoxycortisol, whereas corticosterone was the major product from progesterone. The foetal adrenal, on the other hand, yielded mainly progesterone from pregnenolone with only a small conversion to the corticosteroids. The substrate, progesterone, was transformed, in the main, to 11-deoxycorticosterone. No 3β-hydroxysteroid sulphokinase-transferase activity was demonstrated in either tissue. The importance of these findings and the probable pathways involved in the formation of the biosynthetic products are discussed.

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K J Fowler, L H Wong, B K Griffiths, M C Sibson, S Reed, and K H A Choo

Centromere protein B is a highly conserved constitutive protein found at centromeres. Gene knockout studies in mice have unexpectedly identified Cenpb as a candidate gene involved in uterine function. The present study further explores the role of Cenpb in mice by intermating Cenpb-null mice over several generations. Breeding studies and analysis of uterine tissue indicate that Cenpb-null mice lose reproductive fitness over a number of generations due to a significant reduction in endometrial glands. These results suggest that Cenpb may play an important function in the short- and long-term maintenance of uterine integrity.

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Richard M Griffiths IV, Cindy A Pru, Susanta K Behura, Andrea R Cronrath, Melissa L McCallum, Nicole C Kelp, Wipawee Winuthayanon, Thomas E Spencer, and James K Pru

We previously demonstrated that 5′-AMP-activated protein kinase (AMPK) is essential for normal reproductive functions in female mice. Conditional ablation of Prkaa1 and Prkaa2, genes that encode the α1 and α2 catalytic domains of AMPK, resulted in early reproductive senescence, faulty artificial decidualization, uterine inflammation and fibrotic postparturient endometrial regeneration. We also noted a delay in the timing of embryo implantation in Prkaa1/2d/d female mice, suggesting a role for AMPK in establishing uterine receptivity. As outlined in new studies here, conditional uterine ablation of Prkaa1/2 led to an increase in ESR1 in the uteri of Prkaa1/2d/d mice, resulting in prolonged epithelial cell proliferation and retention of E2-induced gene expression (e.g. Msx1, Muc1, Ltf) through the implantation window. Within the stromal compartment, stromal cell proliferation was reduced by five-fold in Prkaa1/2d/d mice, and this was accompanied by a significant decrease in cell cycle regulatory genes and aberrant expression of decidualization marker genes such as Hand2, Bmp2, Fst and Inhbb. This phenotype is consistent with our prior study, demonstrating a failure of the Prkaa1/2d/d uterus to undergo decidualization. Despite these uterine defects, ovarian function seemed to be normal following ablation of Prkaa1/2 from peri-ovulatory follicles in which ovulation, luteinization and serum progesterone levels were not different on day 5 of pregnancy or pseudopregnancy between Prkaa1/2fl/fl and Prkaa1/2d/d mice. These cumulative findings demonstrate that AMPK activity plays a prominent role in mediating several steroid hormone-dependent events such as epithelial cell proliferation, uterine receptivity and decidualization as pregnancy is established.